Hybrid inorganic/organic materials having novel surface modification; process for the preparation of inorganic/organic hybrid materials; and use of said particles for chromatographic separations

ABSTRACT

The present invention provides novel chromatographic materials, e.g., for chromatographic separations, processes for their preparation and separations devices containing the chromatographic materials. The preparation of the inorganic/organic hybrid materials of the invention wherein a surrounding material is condensed on a porous hybrid core material will allow for families of different hybrid packing materials to be prepared from a single core hybrid material. Differences in hydrophobicity, ion-exchange capacity, surface charge or silanol activity of the surrounding material may be used for unique chromatographic separations of small molecules, carbohydrates, antibodies, whole proteins, peptides, and/or DNA.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.13/266,166 filed Nov. 17, 2011, which is the National Stage ofInternational Application of International Patent Application No.PCT/US2010/036835 filed Jun. 1, 2010, which claims priority to and thebenefit of US Provisional Application So. 61/183,075 filed Jun. 1, 2009.The entire disclosures of the aforementioned patent applications areincorporated herein by this reference.

BACKGROUND OF THE INVENTION

Packing materials for liquid chromatography (LC) are generallyclassified into two types: organic materials, e.g., polydivinylbenzene,and inorganic materials typified by silica. Many organic materials arechemically stable against strongly alkaline and strongly acidic mobilephases, allowing flexibility in the choice of mobile phase pH. However,organic chromatographic materials generally result in columns with lowefficiency, particularly with low molecular-weight analytes. Manyorganic chromatographic materials not only lack the mechanical strengthof typical chromatographic silicas and also shrink and swell when thecomposition of the mobile phase is changed.

Silica is the material most widely used in High Performance LiquidChromatography (HPLC). The most common applications employ silica thathas been surface-derivatized with an organic functional group such asoctadecyl (C18), octyl (C8), phenyl, amino, cyano, etc. As stationaryphases for HPLC, these packing materials result in columns that havehigh efficiency and do not show evidence of shrinking or swelling.

There remains a need for alternative materials that provide additionalmechanical strength, increased column efficiency, and chromatographicselectivity.

SUMMARY OF THE INVENTION

The present invention provides novel chromatographic materials, e.g.,for chromatographic separations, processes for its preparation andseparations devices containing the chromatographic material. Thepreparation of the inorganic/organic hybrid materials of the inventionwherein a surrounding material is condensed on a porous hybrid corematerial will allow for families of different hybrid packing materialsto be prepared from a single core hybrid material. Differences inhydrophobicity, ion-exchange capacity, surface charge or silanolactivity of the surrounding material may be used for uniquechromatographic separations of small molecules, carbohydrates,antibodies, whole proteins, peptides, and/or DNA. In addition, byganosiloxane (POS) with functional groups (e.g., pendant alkyl amines,alcohols, carboxylic acids, alkene or cyano group) that are relevant fora given chromatographic application, new hybrid materials may beprepared that have synthetically useful pendant groups near the surfaceof the particles.

Thus in one aspect, the invention provides an inorganic/organic hybridmaterial comprising an inorganic/organic hybrid surrounding material andan inorganic/organic hybrid core.

In certain aspects, the inorganic/organic hybrid surrounding materialand the inorganic/organic hybrid core are composed of differentmaterials. In other aspects the inorganic/organic hybrid surroundingmaterial and the inorganic/organic hybrid core are composed of the samematerials.

In yet other aspects the inorganic/organic hybrid surrounding materialis composed of a material which enhances one or more of thecharacteristics selected from the group consisting of chromatographicselectivity, column chemical stability, column efficiency, andmechanical strength.

Similarly, in other aspects, the inorganic/organic hybrid core iscomposed of a material which enhances one or more characteristicsselected from the group consisting of chromatographic selectivity,column chemical stability, column efficiency, and mechanical strength.

In other aspects, the inorganic/organic surrounding material is composedof a material which provides a change in hydrophilic/lipophilic balance(HLB), surface charge (e.g., isoelectric point or silanol pKa), and/orsurface functionality for enhanced chromatographic separation.

In still other aspects, the inorganic/organic hybrid surroundingmaterial is independently derived from condensation of one or morepolymeric organofunctional metal precursors, and/or polymeric metaloxide precursors on the surface of the hybrid core, or application ofpartially condensed polymeric organofunctional metal precursors, amixture of two or more polymeric organofunctional metal precursors, or amixture of one or more polymeric organofunctional metal precursors witha polymeric metal oxide precursor(s) on the surface of the hybrid core.

In certain aspects, the inorganic portion of the inorganic/organichybrid surrounding material is independently selected from the groupconsisting of alumina, silica, titania, cerium oxide, or zirconiumoxides, and ceramic materials.

In still other aspects, the inorganic/organic hybrid surroundingmaterial is independently derived from condensation of one or moreorganofunctional silanes and/or tetraalkoxysilane on the surface of thehybrid core, or application of partially condensed organofunctionalsilane, a mixture of two or more organofunctional silanes, or a mixtureof one or more organofunctional silanes with a tetraalkoxysilane (i.e.,tetraethoxysilane, tetramethoxysilane) on the surface of the hybridcore.

In some aspects, the inorganic/organic hybrid surrounding material maybe independently porous or nonporous. Furthermore, the pore structure ofthe inorganic/organic hybrid surrounding material may independentlypossess or not possess an ordered pore structure. In certain aspects,the inorganic/organic hybrid surrounding material may have achromatographically enhancing pore geometry (CEPG).

In other aspects, the inorganic/organic hybrid surrounding material mayindependently comprise from 0-100 mol % hybrid material. In specificaspects, the inorganic portion of the inorganic/organic hybridsurrounding material may independently be present in an amount rangingfrom about 0 molar % to not more than about 25 molar %, wherein thepores of the inorganic/organic hybrid surrounding material aresubstantially disordered. Similarly, the inorganic portion of theinorganic/organic hybrid surrounding material may independently bepresent in an amount ranging from about 25 molar % to not more thanabout 50 molar %, wherein the pores of the inorganic/organic hybridsurrounding material are substantially disordered, and wherein theinorganic/organic hybrid surrounding material independently possesses achromatographically enhancing pore geometry (CEPG).

In some aspects, the inorganic/organic hybrid surrounding material maycomprise a material of formula I:

(SiO₂)_(d)[R²((R)_(p)(R¹)_(q)SiO_(t))_(m)];  (I)

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

p and q are each independently 0.0 to 3.0;

t is 0.5, 1.0, or 1.5;

d is 0 to about 30;

m is an integer from 1-20; wherein R, R¹ and R² are optionallysubstituted; provided that:

(1) when R² is absent, m=1 and

${t = \frac{\left( {4 - \left( {p + q} \right)} \right)}{2}},$

when 0<p+q≤3; and

(2) when R² is present, m=2-20 and

${t = \frac{\left( {3 - \left( {p + q} \right)} \right)}{2}},$

when p+q≤2.

In other aspects, the inorganic/organic hybrid surrounding material maycomprise a material of formula II:

(SiO₂)_(d)[(R)_(p)(R¹)_(q)SiO_(t)]  (II);

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

d is 0 to about 30;

p and q are each independently 0.0 to 3.0, provided that when p+q=1 thent=1.5; when p+q=2 then t=1; or when p+q=3 then t=0.5.

In still other aspects, the inorganic/organic hybrid surroundingmaterial may comprise a material of formula III:

(SiO₂)_(d)/[R²((R¹)_(r)SiO_(t))_(m)]  (III)

wherein,

R¹ is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₉ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

d is 0 to about 30;

r is 0, 1 or 2, provided that when r=0 then t=1.5; or when r=1 then t=1;or when r=2 then t=0.5; and

m is an integer from 1-20.

In yet aspects, the inorganic/organic hybrid surrounding material maycomprise a material of formula IV:

(A)x(B)y(C)z  (IV),

wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat unit which is bonded to one or more repeatunits B or C via an inorganic siloxane bond and which may be furtherbonded to one or more repeat units A or B via an organic bond;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+z=1. In certain embodiments, when z=0, then 0.002≤x/y≤210, and whenz≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In still yet other aspects, the inorganic/organic hybrid surroundingmaterial may comprise a material of formula V:

(A)x(B)y(B*)y*(C)z  (V),

wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat units which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond;

B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or B* or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+z=1. In certain embodiments, when z=0, then 0.002≤x/(y+y*)≤210, andwhen z≠0, then 0.0003≤(y+y*)/z≤500 and 0.002≤x/(y+y*+z)≤210.

In some aspects, the hybrid content of the hybrid core ranges from 1-100mol % hybrid or from 4-100 mol % hybrid. In certain aspects, thestructure of the hybrid core may independently possess or not possess acopolymeric structure. Similarly, the pore structure of the hybrid coremay independently to possess or not possess an ordered pore structure.In certain aspects, the hybrid core may be porous or non-porous.

In some aspects, the hybrid core has formula I:

(SiO₂)_(d)[R²((R)_(p)(R¹)_(q)SiO_(t))_(m)];  (I)

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

p and q are each independently 0.0 to 3.0;

t is 0.5, 1.0, or 1.5;

d is 0 to about 30;

m is an integer from 1-20; wherein R, R¹ and R² are optionallysubstituted;

provided that:

(1) when R² is absent, m=1 and

${t = \frac{\left( {4 - \left( {p + q} \right)} \right)}{2}},$

when 0<p+q≤3; and

(2) when R² is present, m=2-20 and

${t = \frac{\left( {3 - \left( {p + q} \right)} \right)}{2}},$

when p+q≤2.

In other aspects, the hybrid core has formula II:

(SiO₂)_(d)[(R)_(p)(R¹)_(q)SiO_(t)]  (II);

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

d is 0 to about 30;

p and q are each independently 0.0 to 3.0, provided that when p+q=1 thent=1.5; when p+q=2 then t=1; or when p+q=3 then t=0.5.

In still other aspects, the hybrid core has formula III:

(SiO₂)_(d)/[R²((R¹)_(r)SiO_(t))_(m)]  (III)

wherein,

R¹ is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

d is 0 to about 30;

r is 0, 1 or 2, provided that when r=0 then t=1.5; or when r=1 then t=1;or when r=2 then t=0.5; and

m is an integer from 1-20.

In still yet other aspects, the hybrid core has formula IV:

(A)x(B)y(C)z  (IV),

wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat unit which is bonded to one or more repeatunits B or C via an inorganic siloxane bond and which may be furtherbonded to one or more repeat units A or B via an organic bond;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+z=1. In certain embodiments, when z=0, then 0.002≤x/y≤210, and whenz≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In yet other aspects, the hybrid core has formula V:

(A)x(B)y(B*)y*(C)z  (V),

wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat units which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond;

B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or B* or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+z=1. In certain embodiments, when z=0, then 0.002≤x/(y+y*)≤210, andwhen z≠0, then 0.0003≤(y+y*)/z≤500 and 0.002≤x/(y+y*+z)≤210.

In certain aspects, the invention provides an inorganic/organic hybridmaterial wherein the hybrid core and/or the inorganic/organic hybridsurrounding material is a porous hybrid inorganic/organic materialcomprising ordered domains have formula IV, V or VI below:

(A)_(x)(B)_(y)(C)_(z)  (Formula IV)

wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat unit which is bonded to one or more repeatunits B or C via an inorganic siloxane bond and which may be furtherbonded to one or more repeat units A or B via an organic bond;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or C via an inorganic bond; and

-   -   x, y are positive numbers and z is a non negative number,        wherein x+y+z=1. In certain embodiments, when z=0, then        0.002≤x/y≤210, and when z≠0, then

0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210;

(A)_(x)(B)_(y)(B*)_(y*)(C)_(z)  (Formula V)

wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat units which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond;

B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or B* or C via an inorganic bond; and

-   -   x, y are positive numbers and z is a non negative number,        wherein x+y+z=1. In certain embodiments, when z=0, then        0.002≤x/(y+y*)≤210, and when z≠0, then 0.0003≤(y+y*)/z≤500 and        0.002≤x/(y+y*+z)≤210; or

[A]_(y)[B]_(x)  (Formula VI),

-   -   -   wherein x and y are whole number integers and A is

SiO₂/(R¹ _(p)R² _(q)SiO_(t))_(n) or SiO₂/[R³(R¹ _(r)SiO_(t))_(m)]_(n);

-   -   -   wherein R¹ and R² are independently a substituted or            unsubstituted C₁ to C₇ alkyl group, or a substituted or            unsubstituted aryl group, R³ is a substituted or            unsubstituted C₁ to C₇ alkyl, alkenyl, alkynyl, or arylene            group bridging two or more silicon atoms, p and q are 0, 1,            or 2, provided that p+q=1 or 2, and that when p+q=1, t=1.5,            and when p+q=2, t=1; r is 0 or 1, provided that whenr=0,            t=1.5, and when r=1, t=1; m is an integer greater than or            equal to 2; and n is a number from 0.01 to 100;        -   B is:

SiO₂/(R⁴,SiO_(t)).

-   -   -   wherein R is hydroxyl, fluorine, alkoxy, aryloxy,            substituted siloxane, protein, peptide, carbohydrate,            nucleic acid, or combinations thereof, R is not R¹, R², or            R³; v is 1 or 2, provided that when v=1, t=1.5, and when            v=2, t=1; and n is a number from 0.01 to 100;        -   wherein the material of formula VI has an interior area and            an exterior surface, and said interior area of said material            has a composition represented by A; said exterior surface of            said material has a composition represented by A and B, and            wherein said exterior composition is between about 1 and            about 99% of the composition of B and the remainder            comprising A.

In some aspects, the invention provides an inorganic/organic hybridmaterial in which the hybrid core is a monolith, a particle, a sphericalparticle, or a pellicular particle.

In other aspects, the invention provides an inorganic/organic hybridmaterial which has been surface modified by coating with a polymer. Incertain aspects, the inorganic/organic hybrid material has been surfacemodified with a surface modifier having the formula Z_(a)(R¹)_(b)Si—R″,where Z=Cl, Br, I, C₁-C₅ alkoxy, dialkylamino ortrifluoromethanesulfonate; a and b are each an integer from 0 to 3provided that a+b=3; R′ is a C₁-C₆ straight, cyclic or branched alkylgroup, and R″ is a functionalizing group.

In certain aspects, the invention provides an inorganic/organic hybridmaterial further comprising a nanoparticle dispersed within the hybridcore and/or the inorganic/organic hybrid surrounding material. In otheraspects, the nanoparticle may be a mixture of more than one nanoparticleand may be crystalline or amorphous. In still other aspects, thenanoparticle may be silicon carbide, aluminum, diamond, cerium, carbonblack, carbon nanotubes, zirconium, barium, cerium, cobalt, copper,europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium,zinc, boron, oxides thereof, and nitrides thereof.

In another aspect, the invention provides, an inorganic/organic hybridparticle comprising a hybrid particle core with an inorganic/organichybrid surrounding material wherein said particle has the formula

(Y(CH₂)_(n)SiO_(1.5))_(x)(O_(1.5)SiCH₂CH₂SiO_(1.5))_(y)(SiO₂)_(z)

wherein:

each Y is independently —OH, —NH₂, —NR₂, —NR₂R′⁺, SH, S(O)₀₋₂R,S(O)₀₋₂O, C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl,C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy,or C₁-C₁₈ heteroarylaryl, C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

each R and R¹ are independently C₁-C₁₈alkoxy, C₁-C₁₈alkyl, C₁-C₁₈alkyl,C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

n is from 0 to 18;

x, y and z are independently from about 0.0 to about 1.0 wherein y+z is1.0−x and y is from about 3.0 to about 5.0 times greater than z.

In certain aspects, Y is —OH and n is 3. In other aspects, x is 1.0. Instill other aspects Y is —OH, n is 3 and x is 1.0. In still otheraspects n is from 3 to 12, or from 3 to 8.

In another aspect, the invention provides a method for preparing aninorganic/organic hybrid material comprising an inorganic/organic hybridcore and an inorganic/organic hybrid surrounding material comprising thesteps of:

providing a hybrid core material; and

condensing one or more polymeric organofunctional metal precursors,and/or polymeric metal oxide precursors on the surface of the hybridcore.

In still another aspect, the invention provides a method for preparingan inorganic/organic hybrid material comprising an inorganic/organichybrid core and an inorganic/organic hybrid surrounding materialcomprising the steps of:

providing a hybrid core material;

applying a partially condensed polymeric organofunctional metalprecursors, a mixture of two or more polymeric organofunctional metalprecursors, or a mixture of one or more polymeric organofunctional metalprecursors with a polymeric metal oxide on the surface of the hybridcore; and further condensing said surface.

In another aspect, the invention provides a method for preparing aninorganic/organic hybrid material comprising an inorganic/organic hybridcore and an inorganic/organic hybrid surrounding material comprising thesteps of:

providing a hybrid core material; and

condensing one or more polymeric organofunctional metal precursors,and/or polymeric metal oxide precursors on the surface of the hybridcore.

In yet another aspect, the invention provides a method for preparing aninorganic/organic hybrid material comprising an inorganic/organic hybridcore and an inorganic/organic hybrid surrounding material comprising thesteps of:

providing a hybrid core material;

applying a partially condensed polymeric organofunctional metalprecursors, a mixture of two or more polymeric organofunctional metalprecursors, or a mixture of one or more polymeric organofunctional metalprecursors with a polymeric metal oxide on the surface of the hybridcore; and

further condensing said surface.

In certain aspects, the hybrid core material utilized in the methods ofproducing a hybrid material may be provided by the steps of:

a) hydrolytically condensing one or more monomers selected from thegroup consisting of organoalkoxysilanes and tetraalkoxysilanes, with oneor more monomers selected from the group consisting oforganoalkoxysilanes, tetraalkoxysilanes, metal oxide precursors andceramic precursors, to produce a polyorganoalkoxysiloxane;

b) further condensing the polyorganoalkoxysiloxane to form a sphericalporous particle; and

c) subjecting the resulting particle to hydrothermal treatment;

to thereby produce a porous inorganic/organic hybrid core material.

In other aspects, the hybrid core material utilized in the methods ofproducing a hybrid material may be provided by the steps of:

(a) hydrolytically condensing an alkenyl-functionalized organosilanewith a tetraalkoxysilane;

(b) copolymerizing the product of step (a) with an organic olefinmonomer; and

(c) further condensing the product of step (b) to form a sphericalporous particle.

In still other aspects, the hybrid core material utilized in the methodsof producing a hybrid material may be provided by the steps of:

(a) copolymerizing an organic olefin monomer with analkenyl-functionalized organosilane; and

(b) hydrolytically condensing the product of step (a) with atetraalkoxysilane in the presence of a non-optically active porogen; and

(c) further condensing the product of step (b) to form a sphericalporous particle.

In other aspects, the invention provides a separations device having astationary phase comprising the inorganic/organic hybrid material of theinvention. In certain aspects, the separations device may be achromatographic column, a thin layer plate, a filtration membrane, asample cleanup device, a solid support, a microchip separation device,or a microtiter plate. In still other aspects, the separations devicemay be useful for solid phase extraction, high pressure liquidchromatography, ultra-high liquid chromatography, combinatorialchemistry, synthesis, biological assays, or mass spectrometry.

In another aspect, the invention provides a chromatographic column,comprising

a) a column having a cylindrical interior for accepting a packingmaterial and

b) a packed chromatographic bed comprising the inorganic/organic hybridmaterial of the invention.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a desorption pore diameter comparison of products 8b, 9b andthe unmodified hybrid core from multi-point N₂ sorption analysis.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides novel chromatographic materials, e.g.,for chromatographic separations, processes for its preparation andseparations devices containing the chromatographic material. Thepreparation of the materials of the invention wherein the surroundingmaterial is condensed on a porous hybrid core material will allow forfamilies of different hybrid packing materials to be prepared from asingle core hybrid material. Differences in hydrophobicity, ion-exchangecapacity, surface charge or silanol activity of the surrounding materialmay be used for unique chromatographic separations of small molecules,carbohydrates, antibodies, whole proteins, peptides, and/or DNA. Inaddition, by selecting a polyorganosiloxane (POS) with functional groups(e.g., pendant alkyl amines, alcohols, carboxylic acids, alkene or cyanogroup) that are relevant for a given chromatographic application, newhybrid materials may be prepared that have synthetically useful pendantgroups near the surface of the particles.

The present invention will be more fully illustrated by reference to thedefinitions set forth below.

Definitions

“Hybrid” includes inorganic-based structures wherein an organicfunctionality is integral to both the internal or “skeletal” inorganicstructure as well as the hybrid material surface. The inorganic portionof the hybrid material may be, e.g., alumina, silica, titanium, cerium,or “Hybrid” includes inorganic-based structures wherein an organicfunctionality is integral to both the internal or “skeletal” inorganicstructure as well as the hybrid material surface. The inorganic portionof the hybrid material may be, e.g., alumina, silica, titanium, cerium,or zirconium oxides, or ceramic material; in a preferred embodiment, theinorganic portion of the hybrid material is silica. As noted above,exemplary hybrid materials are shown in U.S. Pat. Nos. 4,017,528,6,528,167, 6,686,035 and 7,175,913.

“Hybrid core” includes a hybrid material, as defined herein, in the formof a particle, a monolith or another suitable structure which forms theinternal portion of the inorganic/organic hybrid materials comprising aninorganic/organic hybrid surrounding material of the invention.

“Inorganic/organic hybrid surrounding material” includes a hybridmaterial, as defined herein, which surrounds the hybrid core. Theinorganic/organic hybrid surrounding material may surround the hybridcore entirely, thus encapsulating the hybrid core or may only partiallysurround the hybrid core, thus leaving a surface of the hybrid coreexposed at one or more positions on the surface area of the hybrid core.The inorganic/organic hybrid surrounding material may be disposed on orbonded to or annealed to the hybrid core in such a way that a discreteor distinct transition is discernable or may be bound to the hybrid corein such a way as to blend with the surface of the hybrid core resultingin a gradation of materials. and no discrete internal core surface. Incertain embodiments, the inorganic/organic hybrid surrounding materialmay be the same or different from the material of the hybrid core. Incertain embodiments, including those in which the inorganic/organichybrid surrounding material and the inorganic/organic hybrid core arecomposed of the same materials, the surrounding material may exhibitdifferent physical or physiochemical properties, including, but notlimited to, micropore volume, micropore surface area, average porediameter, carbon content or hydrolytic pH stability.

The term “alicyclic group” includes closed ring structures of three ormore carbon atoms. Alicyclic groups include cycloparaffins or naphtheneswhich are saturated cyclic hydrocarbons, cycloolefins, which areunsaturated with two or more double bonds, and cycloacetylenes whichhave a triple bond. They do not include aromatic groups. Examples ofcycloparaffins include cyclopropane, cyclohexane and cyclopentane.Examples of cycloolefins include cyclopentadiene and cyclooctatetraene.Alicyclic groups also include fused ring structures and substitutedalicyclic groups such as alkyl substituted alicyclic groups. In theinstance of the alicyclics such substituents can further comprise alower alkyl, a lower alkenyl, a lower alkoxy, a lower alkylthio, a loweralkylamino, a lower alkylcarboxyl, a nitro, a hydroxyl, —CF3, —CN, orthe like.

The term “aliphatic group” includes organic compounds characterized bystraight or branched chains, typically having between 1 and 22 carbonatoms. Aliphatic groups include alkyl groups, alkenyl groups and alkynylgroups. In complex structures, the chains can be branched orcross-linked. Alkyl groups include saturated hydrocarbons having one ormore carbon atoms, including straight-chain alkyl groups andbranched-chain alkyl groups. Such hydrocarbon moieties may besubstituted on one or more carbons with, for example, a halogen, ahydroxyl, a thiol, an amino, an alkoxy, an alkylcarboxy, an alkylthio,or a nitro group. Unless the number of carbons is otherwise specified,“lower aliphatic” as used herein means an aliphatic group, as definedabove (e.g., lower alkyl, lower alkenyl, lower alkynyl), but having fromone to six carbon atoms. Representative of such lower aliphatic groups,e.g., lower alkyl groups, are methyl, ethyl, n-propyl, isopropyl,2-chloropropyl, n-butyl, sec-butyl, 2-aminobutyl, isobutyl, tert-butyl,3-thiopentyl and the like. As used herein, the term “nitro” means —NO2;the term “halogen” designates —F, —Cl, —Br or —I; the term “thiol” meansSH; and the term “hydroxyl” means —OH. Thus, the term “alkylamino” asused herein means an alkyl group, as defined above, having an aminogroup attached thereto. Suitable alkylamino groups include groups having1 to about 12 carbon atoms, preferably from 1 to about 6 carbon atoms.The term “alkylthio” refers to an alkyl group, as defined above, havinga sulfhydryl group attached thereto. Suitable alkylthio groups includegroups having 1 to about 12 carbon atoms, preferably from 1 to about 6carbon atoms. The term “alkylcarboxyl” as used herein means an alkylgroup, as defined above, having a carboxyl group attached thereto. Theterm “alkoxy” as used herein means an alkyl group, as defined above,having an oxygen atom attached thereto. Representative alkoxy groupsinclude groups having 1 to about 12 carbon atoms, preferably 1 to about6 carbon atoms, e.g., methoxy, ethoxy, propoxy, tert-butoxy and thelike. The terms “alkenyl” and “alkynyl” refer to unsaturated aliphaticgroups analogous to alkyls, but which contain at least one double ortriple bond respectively. Suitable alkenyl and alkynyl groups includegroups having 2 to about 12 carbon atoms, preferably from 1 to about 6carbon atoms.

The term “alkyl” includes saturated aliphatic groups, includingstraight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl(alicyclic) groups, alkyl substituted cycloalkyl groups and cycloalkylsubstituted alkyl groups. In certain embodiments, a straight chain orbranched chain alkyl has 30 or fewer carbon atoms in its backbone, e.g.,C₁-C₃₀ for straight chain or C₃-C₃₀ for branched chain. In certainembodiments, a straight chain or branched chain alkyl has 20 or fewercarbon atoms in its backbone, e.g., C₁-C₂₀ for straight chain or C₃-C₂₀for branched chain, and more preferably 18 or fewer. Likewise, preferredcycloalkyls have from 4-10 carbon atoms in their ring structure and morepreferably have 4-7 carbon atoms in the ring structure. The term “loweralkyl” refers to alkyl groups having from 1 to 6 carbons in the chainand to cycloalkyls having from 3 to 6 carbons in the ring structure.

Moreover, the term “alkyl” (including “lower alkyl”) as used throughoutthe specification and claims includes both “unsubstituted alkyls” and“substituted alkyls”, the latter of which refers to alkyl moietieshaving substituents replacing a hydrogen on one or more carbons of thehydrocarbon backbone. Such substituents can include, for example,halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy,aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl,aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato,phosphinato, cyano, amino (including alkyl amino, dialkylamino,arylamino, diarylamino and alkylarylamino), acylamino (includingalkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino,imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfate,sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido,heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. It willbe understood by those skilled in the art that the moieties substitutedon the hydrocarbon chain can themselves be substituted, if appropriate.Cycloalkyls can be further substituted, e.g., with the substituentsdescribed above. An “aralkyl” moiety is an alkyl substituted with anaryl, e.g., having 1 to 3 separate or fused rings and from 6 to about 18carbon ring atoms, e.g., phenylmethyl (benzyl).

The term “amino,” as used herein, refers to an unsubstituted orsubstituted moiety of the formula —NRaRb, in which Ra and Rb are eachindependently hydrogen, alkyl, aryl, or heterocyclyl, or Ra and Rb,taken together with the nitrogen atom to which they are attached, form acyclic moiety having from 3 to 8 atoms in the ring. Thus, the term“amino” includes cyclic amino moieties such as piperidinyl orpyrrolidinyl groups, unless otherwise stated. An “amino-substitutedamino group” refers to an amino group in which at least one of Ra andRb, is further substituted with an amino group.

The term “aromatic group” includes unsaturated cyclic hydrocarbonscontaining one or more rings. Aromatic groups include 5- and 6-memberedsingle-ring groups which may include from zero to four heteroatoms, forexample, benzene, pyrrole, furan, thiophene, imidazole, oxazole,thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine andpyrimidine and the like. The aromatic ring may be substituted at one ormore ring positions with, for example, a halogen, a lower alkyl, a loweralkenyl, a lower alkoxy, a lower alkylthio, a lower alkylamino, a loweralkylcarboxyl, a nitro, a hydroxyl, —CF3, —CN, or the like.

The term “aryl” includes 5- and 6-membered single-ring aromatic groupsthat may include from zero to four heteroatoms, for example,unsubstituted or substituted benzene, pyrrole, furan, thiophene,imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine,pyridazine and pyrimidine and the like. Aryl groups also includepolycyclic fused aromatic groups such as naphthyl, quinolyl, indolyl andthe like. The aromatic ring can be substituted at one or more ringpositions with such substituents, e.g., as described above for alkylgroups. Suitable aryl groups include unsubstituted and substitutedphenyl groups. The term “aryloxy” as used herein means an aryl group, asdefined above, having an oxygen atom attached thereto. The term“aralkoxy” as used herein means an aralkyl group, as defined above,having an oxygen atom attached thereto. Suitable aralkoxy groups have 1to 3 separate or fused rings and from 6 to about 18 carbon ring atoms,e.g., O-benzyl.

The terms “as made” and “freshmade” are used interchangeably and referto particles obtained after the gelation process but prior tohydrothermal treatment.

The term “ceramic precursor” is intended include any compound thatresults in the formation of a ceramic material.

The term “chiral moiety” is intended to include any functionality thatallows for chiral or stereoselective syntheses. Chiral moieties include,but are not limited to, substituent groups having at least one chiralcenter, natural and unnatural amino-acids, peptides and proteins,derivatized cellulose, macrocyclic antibiotics, cyclodextrins, crownethers, and metal complexes.

The language “chromatographically-enhancing pore geometry” includes thegeometry of the pore configuration of the presently-disclosed materials,which has been found to enhance the chromatographic separation abilityof the material, e.g., as distinguished from other chromatographic mediain the art. For example, a geometry can be formed, selected orconstructed, and various properties and/or factors can be used todetermine whether the chromatographic separations ability of thematerial has been “enhanced”, e.g., as compared to a geometry known orconventionally used in the art. Examples of these factors include highseparation efficiency, longer column life and high mass transferproperties (as evidenced by, e.g., reduced band spreading and good peakshape.) These properties can be measured or observed usingart-recognized techniques. For example, thechromatographically-enhancing pore geometry of the present porousinorganic/organic hybrid particles is distinguished from the prior artparticles by the absence of “ink bottle” or “shell shaped” pore geometryor morphology, both of which are undesirable because they, e.g., reducemass transfer rates, leading to lower efficiencies.

Chromatographically-enhancing pore geometry is found in hybrid materialscontaining only a small population of micropores. A small population ofmicropores is achieved in hybrid materials when all pores of a diameterof about <34 Å contribute less than about 110 m²/g to the specificsurface area of the material. Hybrid materials with such a low microporesurface area (MSA) give chromatographic enhancements including highseparation efficiency and good mass transfer properties (as evidencedby, e.g., reduced band spreading and good peak shape). Micropore surfacearea (MSA) is defined as the surface area in pores with diameters lessthan or equal to 34 Å, determined by multipoint nitrogen sorptionanalysis from the adsorption leg of the isotherm using the BJH method.As used herein, the acronyms “MSA” and “MPA” are used interchangeably todenote “micropore surface area”.

The term “functionalizing group” includes organic functional groupswhich impart a certain chromatographic functionality to achromatographic stationary phase.

The term “heterocyclic group” includes closed ring structures in whichone or more of the atoms in the ring is an element other than carbon,for example, nitrogen, sulfur, or oxygen. Heterocyclic groups can besaturated or unsaturated and heterocyclic groups such as pyrrole andfuran can have aromatic character. They include fused ring structuressuch as quinoline and isoquinoline. Other examples of heterocyclicgroups include pyridine and purine. Heterocyclic groups can also besubstituted at one or more constituent atoms with, for example, ahalogen, a lower alkyl, a lower alkenyl, a lower alkoxy, a loweralkylthio, a lower alkylamino, a lower alkylcarboxyl, a nitro, ahydroxyl, —CF3, —CN, or the like. Suitable heteroaromatic andheteroalicyclic groups generally will have 1 to 3 separate or fusedrings with 3 to about 8 members per ring and one or more N, O or Satoms, e.g. coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl,furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl,benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl,piperidinyl, morpholino and pyrrolidinyl.

The term “metal oxide precursor” is intended include any compound thatcontains a metal and results in the formation of a metal oxide, e.g.,alumina, silica, titanium oxide, zirconium oxide.

The term “monolith” is intended to include a collection of individualparticles packed into a bed formation, in which the shape and morphologyof the individual particles are maintained. The particles areadvantageously packed using a material that binds the particlestogether. Any number of binding materials that are well known in the artcan be used such as, for example, linear or cross-linked polymers ofdivinylbenzene, methacrylate, urethanes, alkenes, alkynes, amines,amides, isocyanates, or epoxy groups, as well as condensation reactionsof organoalkoxysilanes, tetraalkoxysilanes, polyorganoalkoxysiloxanes,polyethoxysiloxanes, and ceramic precursors. In certain embodiments, theterm “monolith” also includes hybrid monoliths made by other methods,such as hybrid monoliths detailed in U.S. Pat. No. 7,250,214; hybridmonoliths prepared from the condensation of one or more monomers thatcontain 0-99 mole percent silica (e.g., SiO2); hybrid monoliths preparedfrom coalesced porous inorganic/organic particles; hybrid monoliths thathave a chromatographically-enhancing pore geometry; hybrid monolithsthat do not have a chromatographically-enhancing pore geometry; hybridmonoliths that have ordered pore structure; hybrid monoliths that havenon-periodic pore structure; hybrid monoliths that have non-crystallineor amorphous molecular ordering; hybrid monoliths that have crystallinedomains or regions; hybrid monoliths with a variety of differentmacropore and mesopore properties; and hybrid monoliths in a variety ofdifferent aspect ratios. In certain embodiments, the term “monolith”also includes inorganic monoliths, such as those described in G.Guiochon/J. Chromatogr. A 1168 (2007) 101-168.

The term “nanoparticle” is a microscopic particle/grain or microscopicmember of a powder/nanopowder with at least one dimension less thanabout 100 nm, e.g., a diameter or particle thickness of less than about100 nm (0.1 mm), which may be crystalline or noncrystalline.Nanoparticles have properties different from, and often superior tothose of conventional bulk materials including, for example, greaterstrength, hardness, ductility, sinterability, and greater reactivityamong others. Considerable scientific study continues to be devoted todetermining the properties of nanomaterials, small amounts of which havebeen synthesized (mainly as nano-size powders) by a number of processesincluding colloidal precipitation, mechanical grinding, and gas-phasenucleation and growth. Extensive reviews have documented recentdevelopments in nano-phase materials, and are incorporated herein byreference thereto: Gleiter, H. (1989) “Nano-crystalline materials,”Prog. Mater. Sci. 33:223-315 and Siegel, R. W. (1993) “Synthesis andproperties of nano-phase materials,” Mater. Sci. Eng. A168:189-197. Incertain embodiments, the nanoparticles comprise oxides or nitrides ofthe following: silicon carbide, aluminum, diamond, cerium, carbon black,carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, and mixtures thereof. In certain embodiments, the nanoparticlesof the present invention are selected from diamonds, zirconium oxide(amorphous, monoclinic, tetragonal and cubic forms), titanium oxide(amorphous, anatase, brookite and rutile forms), aluminum (amorphous,alpha, and gamma forms), and boronitride (cubic form). In particularembodiments, the nanoparticles of the present invention are selectedfrom nano-diamonds, silicon carbide, titanium dioxide (anatase form),cubic-boronitride, and any combination thereof. Moreover, in particularembodiments, the nanoparticles may be crystalline or amorphous. Inparticular embodiments, the nanoparticles are less than or equal to 100mm in diameter, e.g., less than or equal to 50 mm in diameter, e.g.,less than or equal to 20 mm in diameter.

Moreover, it should be understood that the nanoparticles that arecharacterized as dispersed within the composites of the invention areintended to describe exogenously added nanoparticles. This is incontrast to nanoparticles, or formations containing significantsimilarity with putative nanoparticles, that are capable of formation insitu, wherein, for example, macromolecular structures, such asparticles, may comprise an aggregation of these endogenously created.

The term “substantially disordered” refers to a lack of pore orderingbased on x-ray powder diffraction analysis. Specifically, “substantiallydisordered” is defined by the lack of a peak at a diffraction angle thatcorresponds to a d value (or d-spacing) of at least 1 nm in an x-raydiffraction pattern.

“Surface modifiers” include (typically) organic functional groups whichimpart a certain chromatographic functionality to a chromatographicstationary phase. The porous inorganic/organic hybrid particles possessboth organic groups and silanol groups which may additionally besubstituted or derivatized with a surface modifier.

The language “surface modified” is used herein to describe the compositematerial of the present invention that possess both organic groups andsilanol groups which may additionally be substituted or derivatized witha surface modifier. “Surface modifiers” include (typically) organicfunctional groups which impart a certain chromatographic functionalityto a chromatographic stationary phase. Surface modifiers such asdisclosed herein are attached to the base material, e.g., viaderivatization or coating and later crosslinking, imparting the chemicalcharacter of the surface modifier to the base material. In oneembodiment, the organic groups of a hybrid material, e.g., particle,react to form an organic covalent bond with a surface modifier. Themodifiers can form an organic covalent bond to the material's organicgroup via a number of mechanisms well known in organic and polymerchemistry including but not limited to nucleophilic, electrophilic,cycloaddition, free-radical, carbene, nitrene, and carbocationreactions. Organic covalent bonds are defined to involve the formationof a covalent bond between the common elements of organic chemistryincluding but not limited to hydrogen, boron, carbon, nitrogen, oxygen,silicon, phosphorus, sulfur, and the halogens. In addition,carbon-silicon and carbon-oxygen-silicon bonds are defined as organiccovalent bonds, whereas silicon-oxygen-silicon bonds that are notdefined as organic covalent bonds. A variety of synthetictransformations are well known in the literature, see, e.g., March, J.Advanced Organic Chemistry, 3rd Edition, Wiley, New York, 1985.

Inorganic/Organic Hybrid Materials

The invention provides an inorganic/organic hybrid material comprising ainorganic/organic hybrid core and an inorganic/organic surroundingmaterial

The composition of the surrounding material may be varied by one ofordinary skill in the art to provide enhanced chromatographicselectivity, enhanced column chemical stability, enhanced columnefficiency, and/or enhanced mechanical strength. Similarly, thecomposition of the surrounding material provides a change inhydrophilic/lipophilic balance (HLB), surface charge (e.g., isoelectricpoint or silanol pKa), and/or surface functionality for enhancedchromatographic separation.

Furthermore, in some embodiments, the composition of the surroundingmaterial may also provide a surface functionality for available forfurther surface modification.

The surrounding material may be independently derived from

condensation of one or more polymeric organofunctional metal precursors,and/or polymeric metal oxide precursors on the surface of the hybridcore, or

application of partially condensed polymeric organofunctional metalprecursors, a mixture of two or more polymeric organofunctional metalprecursors, or a mixture of one or more polymeric organofunctional metalprecursors with a polymeric metal oxide precursors on the surface of thehybrid core.

In certain aspects, the inorganic portion of the surrounding material isindependently selected from the group consisting of alumina, silica,titania, cerium oxide, or zirconium oxides, and ceramic materials.

Alternatively, the surrounding material may independently derived from

condensation of one or more organofunctional silanes and/ortetraalkoxysilane on the surface of the hybrid core, or

application of partially condensed organofunctional silane, a mixture oftwo or more organofunctional silanes, or a mixture of one or moreorganofunctional silanes with a tetraalkoxysilane (i.e.,tetraethoxysilane, tetramethoxysilane) on the surface of the hybridcore.

The surrounding material may be independently porous or nonporous.Furthermore, the pore structure of the surrounding material mayindependently possess or not possess an ordered pore structure. Incertain aspects, the surrounding material may have a chromatographicallyenhancing pore geometry (CEPG).

In other aspects, the surrounding material may independently comprisefrom about 0-100 mol % hybrid material. The inorganic portion of thesurrounding material may independently be alumina, silica, titaniumoxide, cerium oxide, zirconium oxide or ceramic materials or a mixturethereof.

In specific aspects, the inorganic portion of the surrounding materialmay independently be present in an amount ranging from about 0 molar %to not more than about 25 molar %, wherein the pores of the surroundingmaterial are substantially disordered. Similarly, the inorganic portionof the surrounding material may independently be present in an amountranging from about 25 molar % to not more than about 50 molar %, whereinthe pores of the surrounding material are substantially disordered, andwherein the surrounding material independently possesses achromatographically enhancing pore geometry (CEPG). In certainembodiments, the inorganic portion of the surrounding material mayindependently be present in an amount ranging from about 50 molar % tonot more than about 75 molar %, wherein the pores of the surroundingmaterial are substantially disordered, and wherein the surroundingmaterial independently possesses a chromatographically enhancing poregeometry (CEPG). In still other embodiments, the inorganic portion ofthe surrounding material may independently be present in an amountranging from about 75 molar % to not more than about 100 molar %,wherein the pores of the surrounding material are substantiallydisordered, and wherein the surrounding material independently possessesa chromatographically enhancing pore geometry (CEPG).

In some aspects, the surrounding material may comprise a material offormula I:

(SiO₂)_(d)[R²((R)_(p)(R¹)_(q)SiO_(t))_(m)];  (I)

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

p and q are each independently 0.0 to 3.0;

t is 0.5, 1.0, or 1.5;

d is 0 to about 30;

m is an integer from 1-20; wherein R, R¹ and R² are optionallysubstituted;

provided that:

(1) when R² is absent, m=1 and

${t = \frac{\left( {4 - \left( {p + q} \right)} \right)}{2}},$

when 0<p+q≤3; and

(2) when R² is present, m=2-20 and

${t = \frac{\left( {3 - \left( {p + q} \right)} \right)}{2}},$

when p+q≤2.

In other aspects, the surrounding material may comprise a material offormula II:

(SiO₂)_(d)[(R)_(p)(R¹)_(q)SiO_(t)]  (II);

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

d is 0 to about 30;

p and q are each independently 0.0 to 3.0, provided that when p+q=1 thent=1.5; when p+q=2 then t=1; or when p+q=3 then t=0.5.

In still other aspects, the surrounding material may comprise a materialof formula III:

(SiO₂)_(d)/[R²((R¹)_(r)SiO_(t))_(m)]  (III)

wherein,

R¹ is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

d is 0 to about 30;

r is 0, 1 or 2, provided that when r=0 then t=1.5; or when r=1 then t=1;or when r=2 then t=0.5; and

m is an integer from 1-20.

In yet aspects, the surrounding material may comprise a material offormula IV:

(A)x(B)y(C)z  (IV),

wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat unit which is bonded to one or more repeatunits B or C via an inorganic siloxane bond and which may be furtherbonded to one or more repeat units A or B via an organic bond;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+z=1. In certain embodiments, when z=0, then 0.002≤x/y≤210, and whenz≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In still yet other aspects, the surrounding material may comprise amaterial of formula V:

(A)x(B)y(B*)y*(C)z  (V),

wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block;

A is an organic repeat unit which is covalently bonded to one or morerepeat units A or B via an organic bond;

B is an organosiloxane repeat units which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond;

B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization;

C is an inorganic repeat unit which is bonded to one or more repeatunits B or B* or C via an inorganic bond; and

x and y are positive numbers and z is a non negative number, whereinx+y+y*+z=1. In certain embodiments, when z=0, then 0.002≤x/(y+y*)≤210,and when z≠0, then 0.0003≤(y+y*)/z≤500 and 0.002≤x/(y+y*+z)≤210.

In certain aspects, R² in the formulas presented above may be present orabsent.

In certain aspects, R¹ in the formulas presented above is C₁-C₁₈ alkylgroup substituted by hydroxyl. In still other aspects, R¹ in theformulas presented above is hydroxypropyl. In still other aspects, thehydroxy substituted alkyl group is further functionalized by anisocyanate. In yet other aspects, the isocyanate is Octadecylisocyanate, Dodecyl isocyanate, Pentafluorophenyl isocyanate,4-cyanophenyl isocyanate, 3-cyanophenyl isocyanate, 2-cyanophenylisocyanate, phenyl isocyate, benzyl isocyanate, phenethyl isocyanate ordiphenylethyl isocyante.

In another aspect, the invention provides materials as described hereinwherein the surrounding material further comprises a nanoparticle or amixture of more than one nanoparticles dispersed within the hybrid core.

In certain embodiments, the nanoparticle is present in <20% by weight ofthe nanocomposite, <10% by weight of the nanocomposite, or <5% by weightof the nanocomposite.

In other embodiments, the nanoparticle is crystalline or amorphous andmay be silicon carbide, aluminum, diamond, cerium, carbon black, carbonnanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, oxides thereof, or a nitride thereof. In particular embodiments,the nanoparticle is a substance which comprises one or more moietiesselected from the group consisting of nano-diamonds, silicon carbide,titanium dioxide, cubic-boronitride.

In other embodiments, the nanoparticles may be less than or equal to 200m in diameter, less than or equal to 100 m in diameter, less than orequal to 50 m in diameter, or less than or equal to 20 μm in diameter.

Hybrid Core

The novel inorganic/organic hybrid materials of the invention comprisean inorganic/organic hybrid surrounding material and a porous ornon-porous inorganic/organic hybrid core. The hybrid core may possess ornot possess a copolymeric structure and may or may not possess anordered pore structure (if porous).

Thus, in one aspect, the invention comprises an inorganic/organic hybridcore, wherein the inorganic portion of the hybrid core is present in anamount ranging from about 0 molar % to not more than about 100 molar %,wherein the pores of the core are substantially disordered. In otherembodiments, the inorganic portion of the hybrid core is present in anamount from about 0 molar % to not more than about 75 molar %. In stillother embodiments, the inorganic portion of the hybrid core is presentin an amount from about 0 molar % to not more than about 50 molar %. Inyet other embodiments, the inorganic portion of the hybrid core ispresent in an amount from about 0 molar % to not more than about 25molar %.

In various embodiments of the aforementioned aspect of the invention,the amount of the inorganic portion of the hybrid core ranges from:about 0 molar % to not more than about 1 molar %; about 0 molar % to notmore than about 2 molar %; about 0 molar % to not more than about 3molar %; about 0 molar % to not more than about 4 molar %; about 0 molar% to not more than about 5 molar %; about 0 molar % to not more thanabout 6 molar %; about 0 molar % to not more than about 7 molar %; about0 molar % to not more than about 8 molar %; about 0 molar % to not morethan about 9 molar %; about 0 molar % to not more than about 10 molar %;about 0 molar % to not more than about 11 molar %; about 0 molar % tonot more than about 12 molar %; about 0 molar % to not more than about13 molar %; about 0 molar % to not more than about 14 molar %; about 0molar % to not more than about 15 molar %; about 0 molar % to not morethan about 16 molar %; about 0 molar % to not more than about 17 molar%; about 0 molar % to not more than about 18 molar %; about 0 molar % tonot more than about 19 molar %; about 0 molar % to not more than about20 molar %; about 0 molar % to not more than about 21 molar %; about 0molar % to not more than about 22 molar %; about 0 molar % to not morethan about 23 molar %; about 0 molar % to not more than about 24 molar%; and about 0 molar % to not more than about 25 molar.

In another aspect, the invention provides an inorganic/organic hybridcore, wherein the inorganic portion of the hybrid core is present in anamount ranging from about 0 molar % to not more than about 100 molar %,wherein the pores of the hybrid core are substantially disordered andwherein the hybrid core has a chromatographically enhancing poregeometry (CEPG). In another embodiment, the inorganic portion of thehybrid core is present in an amount ranging from about 25 molar % to notmore than about 50 molar %, wherein the pores of the hybrid core aresubstantially disordered and wherein the hybrid core has achromatographically enhancing pore geometry (CEPG). In otherembodiments, the inorganic portion of the hybrid core is present in anamount ranging from about 50 molar % to not more than about 75 molar %,wherein the pores of the hybrid core are substantially disordered andwherein the hybrid core has a chromatographically enhancing poregeometry (CEPG). In yet other embodiments the inorganic portion of thehybrid core is present in an amount ranging from about 75 molar % to notmore than about 100 molar %, wherein the pores of the hybrid core aresubstantially disordered and wherein the hybrid core has achromatographically enhancing pore geometry (CEPG).

In various embodiments of the aforementioned aspects of the invention,the amount of the inorganic portion of the hybrid core ranges from:about 25 molar % to not more than about 26 molar %; about 25 molar % tonot more than about 27 molar %; about 25 molar % to not more than about28 molar %; about 25 molar % to not more than about 29 molar %; about 25molar % to not more than about 30 molar %; about 25 molar % to not morethan about 31 molar %; about 25 molar % to not more than about 32 molar%; about 25 molar % to not more than about 33 molar %; about 25 molar %to not more than about 34 molar %; about 25 molar % to not more thanabout 35 molar %; about 25 molar % to not more than about 36 molar %;about 25 molar % to not more than about 37 molar %; about 25 molar % tonot more than about 38 molar %; about 25 molar % to not more than about39 molar %; about 25 molar % to not more than about 40 molar %; about 25molar % to not more than about 41 molar %; about 25 molar % to not morethan about 42 molar %; about 25 molar % to not more than about 43 molar%; about 25 molar % to not more than about 44 molar %; about 25 molar %to not more than about 45 molar %; about 25 molar % to not more thanabout 46 molar %; about 25 molar % to not more than about 47 molar %;about 25 molar % to not more than about 48 molar %; about 25 molar % tonot more than about 49 molar %; about 25 molar % to not more than about50 molar %; about 25 molar % to not more than about 100 molar %; about50 molar % to not more than about 100 molar %; about 50 molar % to notmore than about 75 molar %; and about 75 molar % to not more than about100 molar %.

The inorganic portion of the hybrid core may be alumina, silica (SiO₂),titanium oxide, zirconium oxide, or ceramic materials. The hybridmaterials of the invention in which the inorganic portion is SiO₂ isparticularly advantageous. In certain embodiments, the core material maynot be a hybrid core but may be an entirely inorganic core made only ofan inorganic portion.

In one embodiment, the organic content is from about 1 to about 40%carbon. In another embodiment, the organic content is from about 5 toabout 35% carbon. In yet another embodiment, the invention provides aporous inorganic/organic hybrid particle, wherein the organic content isfrom about 25 to about 40% carbon. In a further embodiment, the organiccontent is from about 25 to about 35% carbon. In a further embodiment,the organic content is from about 5 to about 15% carbon.

In one embodiment, the hybrid material of the invention comprises ahybrid core of formula I:

(SiO₂)_(d)/[R²((R)_(p)(R¹)_(q)SiO_(t))_(m)]  (I)

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₉ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

p and q are each independently 0.0 to 3.0,

t is 0.5, 1.0, or 1.5;

d is 0 to about 30;

m is an integer from 1-20; wherein R, R¹ and R² are optionallysubstituted; provided that: (1) when R² is absent, m=1 and

${t = \frac{\left( {4 - \left( {p + q} \right)} \right)}{2}},$

when 0<p+q≤3; and

(2) when R² is present, m=2-20 and t=(3(p+q)), when p+q<2.

In certain embodiments, R² is absent, t=1.5 when p+q=1; or t=1 whenp+q=2. In other embodiments, R² is present, p=0, q is 0 or 1 and t=1.5when q=0; or t=1 when q=1.

In certain embodiments, R² is absent. In other embodiments, R² ispresent. In embodiments of formula I in which R² is present, theinvention comprises a hybrid core of formula I, wherein p is 0, q is 0,t is 1.5, m is 2, and R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₅ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, orC₁-C₁₈ heteroaryl; wherein each R² is attached to two or more siliconatoms. In a further embodiment, d is 0. In another embodiment, d is0.11. In still another embodiment, d is 0.33. In certain embodiments, dis 0.83.

In other embodiments of formula I in which R² is present, the inventioncomprises a hybrid core of formula I, wherein d is 0, q is 0, and R² isC₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₅ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, or C₁-C₁₈ heteroaryl; and wherein each R²is attached to two or more silicon atoms. In a further embodiment, p is0, 1, or 2. In another further embodiment, t is 1.0 or 1.5. In anotherembodiment, m is 1 or 2.

Certain preferred embodiments of hybrid cores of formula I in which R²is present are set forth in the following table (product numbers referto the numbers used in the examples set forth below):

Product In Reference Reference Formula d p q t m US 6686035 3i(SiO2)_(0.96)(O_(1.5)SiCH₂ − 27 0 0 1.5 2 CH₂SiO_(1.5))_(0.04) US6686035 3j (SiO2)_(0.89)(O_(1.5)SiCH₂ − 8 0 0 1.5 2 CH₂SiO_(1.5))_(0.11)US 6686035 3k (SiO2)_(0.85)(O_(1.5)SiCH₂ − 4 0 0 1.5 2CH₂SiO_(1.5))_(0.2) US 6686035 3l (SiO2)_(0.66)(O_(1.5)SiCH₂ − 2 0 0 1.52 CH₂SiO_(1.5))_(0.33) US 6686035 3n (SiO2)_(0.5)(O_(1.5)SiCH₂ − 1 0 01.5 2 CH₂SiO_(1.5))_(0.5) WO 2008/103423 13a (SiO2)_(0.45)(O_(1.5)SiCH₂− 0.83 0 0 1.5 2 CH₂SiO_(1.5))_(0.55) WO 2008/103423 13b,(SiO2)_(0.25)(O_(1.5)SiCH₂ − 0.33 0 0 1.5 2 13d-13g CH₂SiO_(1.5))_(0.75)WO 2008/103423 13c (SiO2)_(0.1)(O_(1.5)SiCH₂ − 0.11 0 0 1.5 2CH₂SiO_(1.5))_(0.9) WO 2008/103423 5h (O_(1.5)SiCH₂CH₂SiO_(1.5)) 0 0 01.5 2 WO 2008/103423 11a-i, (O_(1.5)SiCH₂CH₂SiO_(1.5))_(x) − 0 0, 1 01.5, 2, 1 l-q, t (YSiO_(1.5))_(1−x) 1.5 WO 2008/103423 11j(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x) − 0 0, 1, 1 0, 0, 0 1.5, 2, 1, 1(YSiO_(1.5))_(w)(ZSiO_(1.5))_(1−x−w) 1.5, 1.5 WO 2008/103423 11k, s(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x) − 0 0, 0 0, 0 1.5, 2, 2 A1(O_(1.5)Si-Y-SiO_(1.5))_(1−x) 1.5 WO 2008/103423 11e(O_(1.5)SiCH₂CH₂SiO_(1.5))_(x) − 0 0, 2 0, 0 1.5, 2, 1 A1 (Y₂SiO₁)_(1−x)1.0 WO 2008/103423 11r (O_(1.5)SiCH₂CH₂SiO_(1.5))_(x) − 0 0, 0 0, 0 1.5,2, 1 A1 (FSiO_(1.5))_(1−x) 1.5

In another embodiment, the hybrid material of the invention comprises ahybrid core of formula II:

(SiO₂)_(d)/[(R)_(p)(R¹)_(q)SiO_(t)]  (II)

wherein,

R and R¹ are each independently C₁-C₁₈ alkoxy, C₁-C₁₈alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl;

d is 0 to about 30;

p and q are each independently 0.0 to 3.0, provided that when p+q=1 thent=1.5; when p+q=2 then t=1; or when p+q=3 then t=0.5.

In yet another embodiment, the hybrid material of the inventioncomprises a hybrid core of formula III:

(SiO₂)_(d)/[R²((R¹)_(q)SiO_(t))_(m)]  (III)

wherein,

R¹ is C₁-C₁₈alkoxy, C₁-C₁₈alkyl, C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl;

R² is C₁-C₁₈alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; or absent;wherein each R² is attached to two or more silicon atoms;

d is 0 to about 30;

r is 0, 1 or 2, provided that when r=0 then t=1.5; when r=1 then t=1; orwhen r=2, then t=0.5; and

m is an integer from 1-20.

In various embodiments, the invention comprises a hybrid core offormulas I and II, wherein R is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, or C₁-C₁₈alkyl. In various embodiments, the invention comprises a hybrid core offormulas I, II and III, wherein R¹ is C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, orC₁-C₁₈ alkyl. In various embodiments, the invention comprises a hybridcore of formulas I and III, wherein R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl,C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl,or C₁-C₁₈ heteroaryl.

In yet another embodiment, the hybrid material of the inventioncomprises a hybrid core of formula IV:

(A)_(x)(B)_(y)(C)_(z)  (IV)

wherein the order of repeat units A, B, and C may be random, block, or acombination of random and block; A is an organic repeat unit which iscovalently bonded to one or more repeat units A or B via an organicbond; B is an organosiloxane repeat unit which is bonded to one or morerepeat units B or C via an inorganic siloxane bond and which may befurther bonded to one or more repeat units A or B via an organic bond; Cis an inorganic repeat unit which is bonded to one or more repeat unitsB or C via an inorganic bond; x and y are positive numbers, and z is anon negative number, wherein x+y+z=1. In certain embodiments, z=0, then0.002≤x/y≤210, and when z≠0, then 0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In a related embodiment, the hybrid material of the invention maycomprise a hybrid core of formula V:

(A)_(x)(B)_(y)(B*)_(y*)(C)_(z)  (V)

wherein the order of repeat units A, B, B*, and C may be random, block,or a combination of random and block; A is an organic repeat unit whichis covalently bonded to one or more repeat units A or B via an organicbond; B is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond and which maybe further bonded to one or more repeat units A or B via an organicbond, B* is an organosiloxane repeat unit which is bonded to one or morerepeat units B or B* or C via an inorganic siloxane bond, wherein B* isan organosiloxane repeat unit that does not have reactive (i.e.,polymerizable) organic components and may further have a protectedfunctional group that may be deprotected after polymerization; C is aninorganic repeat unit which is bonded to one or more repeat units B orB* or C via an inorganic bond; x and y are positive numbers and z is anon negative number, wherein x+y+z=1. In certain embodiments, when z=0,then 0.002≤x/(y+y*)≤210, and when z≠0, then 0.0003≤(y+y*)/z≤500 and0.002≤x/(y+y*+z)≤210.

Repeat unit A may be derived from a variety of organic monomer reagentspossessing one or more polymerizable moieties, capable of undergoingpolymerization, e.g., a free radical-mediated polymerization. A monomersmay be oligomerized or polymerized by a number of processes andmechanisms including, but not limited to, chain addition and stepcondensation processes, radical, anionic, cationic, ring-opening, grouptransfer, metathesis, and photochemical mechanisms.

A may also be one of the following:

wherein each R is independently H or a C₁-C₁₀ alkyl group (e.g, methyl,ethyl, or propyl); m is an integer of from 1 to about 20; n is aninteger of from 0 to 10; and Q is hydrogen, N(C₁₋₆alkyl)₃,N(C₁₋₆alkyl)₂(C₁₋₆alkyl-SO₃), or C(C₁₋₆hydroxyalkyl)₃.

Repeat unit B may be derived from several mixed organic-inorganicmonomer reagents possessing two or more different polymerizablemoieties, capable of undergoing polymerization, e.g., a freeradical-mediated (organic) and hydrolytic (inorganic) polymerization. Bmonomers may be oligomerized or polymerized by a number of processes andmechanisms including, but not limited to, chain addition and stepcondensation processes, radical, anionic, cationic, ring-opening, grouptransfer, metathesis, and photochemical mechanisms.

B may also be one of the following:

Repeat unit C may be —SiO₂— and may be derived from an alkoxysilane,such as tetraethoxysilane (TEOS) or tetramethoxysilane (TMOS).

In one embodiment, A is a substituted ethylene group, B is aoxysilyl-substituted alkyl group, and C is a oxysilyl group, for examplethe following:

A specific embodiment of a porous hybrid core of formula IV is:

wherein

R₁ is H, F, Cl, Br, I, lower alkyl (e.g., CH₃ or CH₂CH₃);

R₂ and R₃ are each independently H, F, Cl, Br, I, alkane, substitutedalkane, alkene, substituted alkene, aryl, substituted aryl, cyano,ether, substituted ether, embedded polar group;

R⁴ and R⁵ are each independently H, F, Cl, Br, I, alkane, substitutedalkane, alkene, substituted alkene, aryl, substituted aryl, ether,substituted ether, cyano, amino, substituted amino, diol, nitro,sulfonic acid, cation or anion exchange groups,

0≤a≤2x, 0≤b≤4, and 0≤c≤4, provided that b+c≤4 when a=1;

1≤d≤20,

0.0003≤y/z≤500 and 0.002≤x/(y+z)≤210.

In still another embodiment, the hybrid cores are spherical. In afurther embodiment, the spherical core has a non-crystalline oramorphous molecular ordering. In a further embodiment, the sphericalcore has a non-periodic pore structure.

In other embodiments, the inorganic/organic hybrid core has a surfacearea of about 40 to 1100 m²/g. In certain instances, the hybrid core hasa surface area of about 80 to 500 m²/g. In other instances, the particlehas a surface area of about 800 to 1100 m²/g.

In one embodiment, the inorganic/organic hybrid core has microporevolumes of about 0.2 to 1.5 cm³/g. In certain instances, the hybrid corehas micropore volumes of about 0.6 to 1.3 cm³/g.

In another embodiment, the inorganic/organic hybrid core has a microporesurface area of less than about 110 m²/g. In certain instances, thehybrid core has a micropore surface area of less than about 105 m²/g. Inother instances, the hybrid core has a micropore surface area of lessthan about 80 m²/g. In still other instances, the hybrid core has amicropore surface area of less than about 50 m²/g.

In one embodiment, the porous inorganic/organic hybrid core has anaverage pore diameter of about 20 to 1000 Å. In a further embodiment,the hybrid core has an average pore diameter of about 30 to 300 Å. Inanother embodiment, the hybrid core has an average pore diameter ofabout 60 to 200 Å. In a further embodiment, the particle has an averagepore diameter of about 80 to 140 Å.

In another embodiment, the hybrid core has an average size of about 0.1m to about 300 m. In a further embodiment, the hybrid core has anaverage size of about 0.1 m to about 30 m.

In certain embodiments, the hybrid core is hydrolytically stable at a pHof about 1 to about 14. In one embodiment, the hybrid core ishydrolytically stable at a pH of about 10 to about 14. In anotherembodiment, the hybrid core is hydrolytically stable at a pH of about 1to about 5.

In one embodiment, the invention comprises an inorganic/organic hybridcore as described herein, wherein the core is formed by hydrolyticcondensation of one or more monomers selected from the group consistingof:

wherein R, R¹ and R² are as defined previously; X is C₁-C₁₈ alkoxy orC₁-C₁₈ alkyl; and n is 1-8.

In a further embodiment, the monomer is 1,2-bis(triethoxysilyl)ethane:

In another further embodiment, the monomer is 1,2-bis(methyldiethoxysilyl)ethane:

or 1,8-bis(triethoxysilyl)octane:

In other embodiment, the porous inorganic/organic hybrid core asdescribed herein has been surface modified with a surface modifierhaving the formula Z_(a)(R¹)_(b)Si—R″, where Z=Cl, Br, I, C₁-C₅ alkoxy,dialkylamino or trifluoromethanesulfonate; a and b are each an integerfrom 0 to 3 provided that a+b=3; R′ is a C₁-C₆ straight, cyclic orbranched alkyl group, and R″ is a functionalizing group.

In another embodiment, the hybrid core has been surface modified bycoating with a polymer.

In certain embodiments, R¹ is selected from the group consisting ofmethyl, ethyl, propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl,isopentyl, hexyl and cyclohexyl. In other embodiments, R is selectedfrom the group consisting of alkyl, alkenyl, alkynyl, aryl, cyano,amino, diol, nitro, ester, a cation or anion exchange group, an alkyl oraryl group containing an embedded polar functionality and a chiralmoiety.

In one embodiment, R″ is a C₁-C₃₀ alkyl group. In a further embodiment,R″ comprises a chiral moiety. In another further embodiment, R″ is aC₁-C₂₀ alkyl group.

In certain embodiments, the surface modifier is selected from the groupconsisting of octyltrichlorosilane, octadecyltrichlorosilane,octyldimethylchlorosilane and octadecyldimethylchlorosilane. Preferably,the surface modifier is selected from the group consisting ofoctyltrichlorosilane and octadecyltrichlorosilane.

In another embodiment, the hybrid core has been surface modified by acombination of organic group and silanol group modification.

In still another embodiment, the hybrid core has been surface modifiedby a combination of organic group modification and coating with apolymer. In a further embodiment, the organic group comprises a chiralmoiety.

In yet another embodiment, the hybrid core has been surface modified bya combination of silanol group modification and coating with a polymer.

In other embodiments, the hybrid core has been surface modified viaformation of an organic covalent bond between the particle's organicgroup and the modifying reagent.

In still other embodiments, the hybrid core has been surface modified bya combination of organic group modification, silanol group modificationand coating with a polymer.

In another embodiment, the hybrid core has been surface modified bysilanol group modification.

In another aspect, the porous inorganic/organic hybrid core has achromatographically enhancing pore geometry, wherein the materialcomprises a combination of the particles described herein.

In certain embodiments, the porous inorganic/organic hybrid core is amonolith.

In another aspect, the invention provides materials as described hereinwherein the hybrid core further comprises a nanoparticle or a mixture ofmore than one nanoparticles dispersed within the hybrid core.

In certain embodiments, the nanoparticle is present in <20% by weight ofthe nanocomposite, <10% by weight of the nanocomposite, or <5% by weightof the nanocomposite.

In other embodiments, the nanoparticle is crystalline or amorphous andmay be silicon carbide, aluminum, diamond, cerium, carbon black, carbonnanotubes, zirconium, barium, cerium, cobalt, copper, europium,gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc,boron, oxides thereof, or a nitride thereof. In particular embodiments,the nanoparticle is a substance which comprises one or more moietiesselected from the group consisting of nano-diamonds, silicon carbide,titanium dioxide, cubic-boronitride.

In other embodiments, the nanoparticles may be less than or equal to 200nm in diameter, less than or equal to 100 nm in diameter, less than orequal to 50 nm in diameter, or less than or equal to 20 nm in diameter.

Surface Modification

The novel inorganic/organic hybrid materials of the invention mayfurther be surface modified.

Thus, in one embodiment, the material as described herein may be surfacemodified with a surface modifier having the formula Z_(a)(R¹)_(b)Si—R″,where Z=Cl, Br, I, C₁-C₅ alkoxy, dialkylamino ortrifluoromethanesulfonate; a and b are each an integer from 0 to 3provided that a+b=3; R′ is a C₁-C₆ straight, cyclic or branched alkylgroup, and R″ is a functionalizing group.

In another embodiment, the materials have been surface modified bycoating with a polymer.

In certain embodiments, R′ is selected from the group consisting ofmethyl, ethyl, propyl, isopropyl, butyl, t-butyl, sec-butyl, pentyl,isopentyl, hexyl and cyclohexyl. In other embodiments, R is selectedfrom the group consisting of alkyl, alkenyl, alkynyl, aryl, cyano,amino, diol, nitro, ester, a cation or anion exchange group, an alkyl oraryl group containing an embedded polar functionality and a chiralmoiety.

In one embodiment, R″ is a C₁-C₃₀ alkyl group. In a further embodiment,R″ comprises a chiral moiety. In another further embodiment, R″ is aC₁-C₂₀ alkyl group.

In certain embodiments, the surface modifier is selected from the groupconsisting of octyltrichlorosilane, octadecyltrichlorosilane,octyldimethylchlorosilane and octadecyldimethylchlorosilane. In someembodiments, the surface modifier is selected from the group consistingof octyltrichlorosilane and octadecyltrichlorosilane. In otherembodiments, the surface modifier is selected from the group consistingof an isocyanate or 1,1′-carbonyldiimidazole (particularly when thehybrid group contains a (CH₂)₃OH group).

In another embodiment, the material has been surface modified by acombination of organic group and silanol group modification.

In still another embodiment, the material has been surface modified by acombination of organic group modification and coating with a polymer. Ina further embodiment, the organic group comprises a chiral moiety.

In yet another embodiment, the material has been surface modified by acombination of silanol group modification and coating with a polymer.

In other embodiments, the material has been surface modified viaformation of an organic covalent bond between the particle's organicgroup and the modifying reagent.

In still other embodiments, the material has been surface modified by acombination of organic group modification, silanol group modificationand coating with a polymer.

In another embodiment, the material has been surface modified by silanolgroup modification.

In certain embodiments, the surface modified layer may be porous ornonporous.

Separation Devices and Kits

Another aspect provides a variety of separations devices having astationary phase comprising the inorganic/organic hybrid materials asdescribed herein. The separations devices include, e.g., chromatographiccolumns, thin layer plates, filtration membranes, sample cleanup devicesand microtiter plates. The separations devices can be used for a varietyof separations techniques including, but not limited to, normal-phaseseparations, reversed-phase separations, HILIC separations, SFCseparations, affinity separations, and SEC separations.

The inorganic/organic hybrid materials impart to these devices improvedlifetimes because of their improved stability. Thus, in a particularaspect, the invention provides a chromatographic column having improvedlifetime, comprising

a) a column having a cylindrical interior for accepting a packingmaterial, and

b) a packed chromatographic bed comprising the inorganic/organic hybridmaterials as described herein.

The invention also provides for a kit comprising the inorganic/organichybrid materials as described herein, as described herein, andinstructions for use. In one embodiment, the instructions are for usewith a separations device, e.g., chromatographic columns, thin layerplates, filtration membranes, sample cleanup devices and microtiterplates.

Synthesis of Materials of the Invention

The invention also provides methods for producing the inorganic/organichybrid materials described herein.

In one embodiment, the invention provides a method for producing theinorganic/organic hybrid materials described herein comprising:

providing a hybrid core material; and

condensing one or more polymeric organofunctional metal precursors,and/or polymeric metal oxide precursors on the surface of the hybridcore.

In another embodiment, the invention provides a method for producing theinorganic/organic hybrid materials described herein comprising:

providing a hybrid core material;

applying a partially condensed polymeric organofunctional metalprecursors, a mixture of two or more polymeric organofunctional metalprecursors, or a mixture of one or more polymeric organofunctional metalprecursors with a polymeric metal oxide on the surface of the hybridcore; and

further condensing said surface.

In certain embodiments, the method producing the inorganic/organichybrid materials described herein further comprises the step ofsubjecting the hybrid material to hydrothermal treatment.

In another embodiment, the invention provides a method for producing theinorganic/organic hybrid materials described herein, comprising thesteps of:

providing a hybrid core material; and

condensing one or more polymeric organofunctional metal precursors,and/or polymeric metal oxide precursors on the surface of the hybridcore.

In another embodiment, the invention provides a method for producing theinorganic/organic hybrid materials described herein comprising the stepsof:

providing a hybrid core material;

applying a partially condensed polymeric organofunctional metalprecursors, a mixture of two or more polymeric organofunctional metalprecursors, or a mixture of one or more polymeric organofunctional metalprecursors with a polymeric metal oxide on the surface of the hybridcore; and

further condensing said surface.

In certain embodiments, the process of producing the inorganic/organichybrid materials described herein as described above further comprisesthe step of subjecting the hybrid material to hydrothermal treatment.

In a particular embodiment, the invention provides methods for producingthe inorganic/organic hybrid materials described herein in which thehybrid core of the materials is provided by the steps of:

a) hydrolytically condensing one or more monomers selected from thegroup consisting of organoalkoxysilanes and tetraalkoxysilanes with oneor more monomers selected from the group consisting oforganoalkoxysilanes, tetraalkoxysilanes, metal oxide precursors, andceramic precursors to produce a polyorganoalkoxysiloxane;

b) further condensing the polyorganoalkoxysiloxane to form a sphericalporous particle; and

c) subjecting the resulting particle to hydrothermal treatment.

In an embodiment of the foregoing method when preparing a hybrid core,comprising the inorganic portion in an amount ranging from about 0 molar% to not more than about 25 molar %, wherein the pores of the particleare substantially disordered, the hydrolytic condensing of one or moremonomers excludes tetraalkoxysilanes. In some embodiments of theforegoing method, the inorganic portion is present in an amount rangingfrom about 0 molar % to not more than about 100 molar %; from 25 molar %to about 50 molar %, from about 50 molar % to about 75 molar %; or fromabout 75 molar % to about 100 molar %; wherein the pores of the particleare substantially disordered, the hydrolytic condensing of one or moremonomers excludes tetraalkoxysilanes.

In one embodiment, the metal oxide precursors of the hybrid cores areselected from the group consisting of the oxide, hydroxide, ethoxide,methoxide, propoxide, isopropoxide, butoxide, sec-butoxide,tert-butoxide, iso-butoxide, phenoxide, ethylhexyloxide,2-methyl-2-butoxide, nonyloxide, isooctyloxide, glycolates, carboxylate,nitrate, chlorides, and mixtures thereof of titanium, zirconium, oraluminum. Preferably, the metal oxide precursors are methyl titaniumtriisopropoxide, methyl titanium triphenoxide, titaniumallylacetoacetatetriisopropoxide, titanium methacrylate triisopropoxide,titanium methacryloxyethylacetoacetate triisopropoxide,pentamethylcyclopentadienyl titanium trimethoxide,pentamethylcyclopentadienyl titanium trichloride, and zirconiummethacryloxyethylacetoacetate tri-n-propoxide.

In another aspect, the invention provides methods for producing thematerials of the invention in which the hybrid core of the materials isprovided by the steps of:

a) hydrolytically condensing one or more monomers selected from thegroup consisting of organoalkoxysilanes and tetraalkoxysilanes, toproduce a polyorganoalkoxysiloxane;

b) further condensing the polyorganoalkoxysiloxane to form a sphericalporous particle; and

c) subjecting the resulting particle to hydrothermal treatment; tothereby produce a porous inorganic/organic hybrid core.

In certain embodiments, the invention provides a method of producing ahybrid core comprising SiO₂ in an amount ranging from about 0 molar % tonot more than about 25 molar %, wherein the pores of the particle aresubstantially disordered, wherein the one or more monomers excludetetraalkoxysilanes. In some embodiments of the foregoing method SiO₂ ispresent in an amount ranging from about 0 molar % to not more than about100 molar %; from 25 molar % to about 50 molar %, from about 50 molar %to about 75 molar %; or from about 75 molar % to about 100 molar %;wherein the pores of the particle are substantially disordered, whereinthe one or more monomers exclude tetraalkoxysilanes.

In still another aspect, the invention provides methods for producingthe materials of the invention in which a hybrid core, comprising SiO₂in an amount ranging from about 0 molar % to not more than about 100molar %, wherein the pores of the particle are substantially disordered,is provided by the steps of:

a) hydrolytically condensing one or more monomers selected from thegroup consisting of organoalkoxysilanes and tetraalkoxysilanes, toproduce a polyorganoalkoxysiloxane;

b) further condensing the polyorganoalkoxysiloxane to form a sphericalporous particle; and

c) subjecting the resulting particle to hydrothermal treatment; tothereby produce a porous inorganic/organic hybrid particle of theinvention.

In certain embodiments, the condensing step comprises treating anaqueous emulsion of the polyorganoalkoxysiloxane with base to form aspherical core.

In another embodiment, the invention provides a method of producing aporous inorganic/organic hybrid core as described above, furthercomprising treating the spherical porous particle with acid.

In still another embodiment, the invention provides a method ofproducing a porous inorganic/organic hybrid core as described above,further comprising treating the aqueous emulsion of thepolyorganoalkoxysiloxane with one or more additional aliquots of base toform a spherical particle. In a further embodiment, the inventionprovides a method further comprising treating the spherical porousparticle with acid.

In certain embodiments, the invention provides a method, wherein thehybrid core has a chromatographically enhancing pore geometry (CEPG).

In one embodiment, the foregoing methods produce the porousinorganic/organic hybrid core having formula I, II, or II describedabove.

In certain embodiments, the invention provides a method, furthercomprising preparing an aqueous suspension of thepolyorganoalkoxysiloxane and gelling in the presence of a base catalystto produce the porous inorganic/organic hybrid core.

In certain embodiments of the method of producing the hybrid core, stepa) or step b) is acid-catalyzed or base-catalyzed. In one embodiment,step a) is acid catalyzed. In another embodiment, step b) is basecatalyzed. In a further embodiment, the base-catalyzed reaction is anoil-in-water emulsification reaction.

Thus, in an advantageous embodiment, step b) of producing the hybridcore further comprises treating an aqueous emulsion of thepolyorganoalkoxysiloxane with base. In a further advantageousembodiment, following treatment with base, the particle produced in stepb) is treated with acid. In an alternative advantageous embodiment, thetreatment of the aqueous emulsion of the polyorganoalkoxysiloxane withbase in step b) is followed by treatment with one or more additionalaliquots of base and then the resulting particles are treated with acid.

Suitable acids for use with the methods of the invention includehydrochloric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid,sulfuric acid, formic acid, acetic acid, trichloroacetic acid,trifluoroacetic acid and phosphoric acid. Suitable bases for use withthe methods of the invention include alkyl amines, ammonium hydroxide,hydroxide salts of the group I and group II metals, carbonate andhydrogen carbonate salts of the group I metals and alkoxide salts of thegroup I and group II metals. Alkyl amines include, e.g., trimethylamine, triethyl amine, diisopropyl ethyl amine, etc. Tris(hydroxymethyl)methylamine is a preferred alkyl amine.

In certain embodiments, steps a) and b) of producing the hybrid core areperformed in a solvent selected from the group consisting of water,methanol, ethanol, propanol, isopropanol, butanol, tert-butanol,pentanol, hexanol, cyclohexanol, hexafluoroisopropanol, cyclohexane,petroleum ethers, diethyl ether, dialkyl ethers, tetrahydrofuran,acetonitrile, ethyl acetate, pentane, hexane, heptane, benzene, toluene,xylene, N,N-dimethylformamide, dimethyl sulfoxide,1-methyl-2-pyrrolidinone, methylene chloride, chloroform andcombinations thereof.

In still another aspect, the invention provides methods for producingthe inorganic/organic hybrid materials described herein in which ahybrid core, of formula IV or formula V, is produced comprising thesteps of:

(a) hydrolytically condensing an alkenyl-functionalized organosilanewith a tetraalkoxysilane;

(b) copolymerizing the product of step (a) with an organic olefinmonomer; and (c) further condensing the product of step (b) to form aspherical porous particle.

In still another aspect, the invention provides methods for producingthe materials of the invention in which a hybrid core, of formula IV orformula V described above, is produced comprising the steps of:

(a) copolymerizing an organic olefin monomer with analkenyl-functionalized organosilane; and

(b) hydrolytically condensing the product of step (a) with atetraalkoxysilane in the presence of a non-optically active porogen; and

(c) further condensing the product of step (b) to form a sphericalporous particle.

In certain embodiments, the copolymerizing step is freeradical-initiated and wherein the hydrolytically condensing step is anacid- or base-catalyzed.

In one embodiment, the invention provides a method as described above,further comprising subjecting the resulting hybrid core to hydrothermaltreatment.

In certain embodiments, the spherical hybrid core produced in step b) orstep c) are sized to generate a particle size distribution that isdistinct from the particle size distribution of the spherical porousparticles produced in step b) or step c).

In other embodiments, the spherical hybrid core has a non-crystalline oramorphous molecular ordering. In a further embodiment, the sphericalhybrid core has a non-periodic pore structure.

In certain embodiments, the invention provides a method of producing thehybrid core of the material of the invention, wherein the hybrid corehas a surface area of about 40 to 1100 m2/g. In a further embodiment,the hybrid core has a surface area of about 80 to 500 m2/g. In anotherfurther embodiment, the hybrid core has a surface area of about 800 to1100 m2/g.

In one embodiment, the invention provides a method of producing thehybrid core of the material of the invention wherein the hybrid core hasmicropore volumes of about 0.2 to 1.5 cm3/g. In a further embodiment,the hybrid core has micropore volumes of about 0.6 to 1.3 cm3/g.

In another embodiment, the invention provides a method of producing thehybrid core of the material of the invention wherein the hybrid core hasa micropore surface area of less than about 110 m²/g. In a furtherembodiment, the hybrid core has a micropore surface area of less thanabout 105 m²/g. In another embodiment, the hybrid core has a microporesurface area of less than about 80 m²/g. In a further embodiment, thehybrid core has a micropore surface area of less than about 50 m²/g.

In another embodiment, the invention provides a method of producing thehybrid core of the material of the invention wherein the hybrid core hasan average pore diameter of about 20 to 500 Å. In a further embodiment,the hybrid core has an average pore diameter of about 30 to 180 Å.

In certain instances, the hybrid core of the material has an averagepore diameter of about 60 to 200 Å. Preferably, the hybrid core has anaverage pore diameter of about 80 to 140 Å.

In other instances, the hybrid core of the material has an average sizeof about 0.1 μm to about 300 μm, preferably about 0.1 μm to about 30 μm.

In another embodiment, the invention provides a method of producing thehybrid core of the material of the invention wherein the hybrid core ishydrolytically stable at a pH of about 1 to about 14.

In certain instances, the hybrid core is hydrolytically stable at a pHof about 10 to about 14. In other instances, the particle ishydrolytically stable at a pH of about 1 to about 5.

In one embodiment, the invention provides a method of producing thehybrid core of the material of the invention wherein the organic contentis from about 25 to about 40% carbon. In a further embodiment, theorganic content is from about 25 to about 35% carbon. In one embodiment,the organic content is from about 1 to about 40% carbon. In anotherembodiment, the organic content is from about 5 to about 35% carbon. Inyet another embodiment, the invention provides a porousinorganic/organic hybrid particle, wherein the organic content is fromabout 25 to about 40% carbon. In a further embodiment, the organiccontent is from about 25 to about 35% carbon. In a further embodiment,the organic content is from about 5 to about 15% carbon.

In certain instances, the invention provides a method of producing thehybrid core of the material of the invention wherein R is C₁-C₁₈ alkoxy,C₁-C₁₈ alkyl, or C₁-C₁₈ alkyl.

In another embodiment, R¹ is C₁-C₁₈ alkoxy C₁-C₁₈ alkyl, or C₁-C₁₈alkyl.

In other embodiments, R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, orC₁-C₁₈ heteroaryl.

In one embodiment, the invention provides a method of producing thehybrid core of formula I wherein p is 0, q is 0, t is 1.5, m is 2, andR² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, or C₁-C₁₈ heteroaryl; wherein eachR² is attached to two or more silicon atoms. In a further embodiment, dis 0. In another further embodiment, d is 0.11.

In still another further embodiment, d is 0.33. In yet another furtherembodiment, d is 0.83.

In another embodiment, the invention provides a method of producing thehybrid core of formula I wherein d is 0, q is 0, and R² is C₁-C₁₈ alkyl,C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈heterocycloalkyl, C₅-C₁₈ aryl, or C₁-C₁₈ heteroaryl; wherein each R² isattached to two or more silicon atoms. In a further embodiment, p is 0,1, or 2. In another embodiment, t is 1.0 or 1.5. In another embodiment,m is 1 or 2.

In one embodiment, the invention provides a method of producing thehybrid core of the invention wherein the one or more monomers areselected from the group consisting of:

wherein R, R¹ and R² are as defined previously; X is C₁-C₁₈ alkoxy orC₁-C₁₈ alkyl; and n is 1-8.

In certain embodiments, the monomer is 1,2-bis(triethoxysilyl)ethane:

In other embodiments, the monomer is 1,2-bis(methyldiethoxysilyl)ethane:

or 1,8-bis(triethoxysilyl)octane:

The freshmade hybrid cores resulting from step b) are advantageouslysized to generate a particle size distribution that is distinct from theparticle size distribution of the freshmade spherical porous particlesresulting from step b). Any number of well-known sizing techniques maybe used. Such sizing techniques are described, for example, in W.Gerhartz, et al. (editors) Ullmann's Encyclopedia of IndustrialChemistry, 5^(th) edition, Volume B2: Unit Operations I, VCHVerlagsgesellschaft mbH, (Weinheim, Fed. Rep. Germ. 1988). Particles areadvantageously sized to a diameter range of about 0.5 μm to about 300μm, more advantageously about 1 μm to about 20 m.

The hybrid cores of the material of the invention can be prepared by theforegoing methods. Further details on the synthesis of the hybrid coresof formulas IV and V can be found, for example, in WO2004/041398-A2.Certain embodiments of the synthesis of the porous inorganic/organichybrid particles of formulas I-III described above are further describedas follows.

Porous spherical particles of hybrid core may, in a preferredembodiment, be prepared by a four-step process. In the first step, anorganoalkoxysilane can be prepolymerized by itself, or with one or moreorganoalkoxysilanes or with 0-49 molar % tetraalkoxysilane such astetraethoxysilane (TEOS) to form a polyorganoalkoxysiloxe (POS) byco-hydrolyzing in the presence of an acid catalyst. A list oforganoalkoxysilanes that may be used in this approach includes (but isnot limited to); bis(triethoxysilyl)ethane; bis(triethoxylsilyl)octane;bis(methyldiethoxysilyl)ethane; bis(triethoxysilyl)ethene;bis(trimethoxysilylethyl)benzene; ethyltriethoxysilane;diethyldiethoxysilane; mercaptopropyltriethoxysilane;methyltriethoxysilane; vinyltriethoxysilane; hexyltriethoxysilane;chloropropyltriethoxysilane; phenylethyltrimethoxysilane;octadecyltrimethoxysilane; octyltrimethoxysilane;3,3.3-trifluoropropyltrimethoxysilane; and 3-cyanobutyltriethoxysilane.The use of reactive organoalkoxysilanes that have been shown to react byprotodesilylation, deprotection, or decompose may also be useful inintroducing porosity into hybrid particles. A list oforganoalkoxysilanes that may protodesilylate, deprotect or decompose tointroduce porosity into hybrid cores includes (but is not limited to);phenyltriethoxysilane; methacryloxypropyltrimethoxysilane;acetyloxyethyltrimethoxysilane, chloroethyltriethoxysilane, andfluorotriethoxysilane.

In the second step, the POS is suspended in an aqueous medium in thepresence of a surfactant or a combination of surfactants and gelled intoporous spherical hybrid cores. The process of gelation can be controlledusing a single addition of base catalyst or multiple additions of basecatalyst, a combination of base and acid catalyst, or the multi-additionof base catalyst followed by acid catalyst.

In the third step, the pore structure of the hybrid cores is modified byhydrothermal treatment, producing an intermediate hybrid product whichmay be used for particular purposes itself, or may be further processedbelow. The above three steps of the process allow much better control ofthe particle sphericity, morphology, pore volume and pore sizes thanthose described in the prior art, and thus provide thechromatography-enhancing pre geometry.

In one embodiment of the invention, the surface organic groups of thehybrid cores and/or the materials may be derivatized or modified in asubsequent step via formation of an organic covalent bond between theparticle's organic group and the modifying reagent. Alternatively, thesurface silanol groups of the hybrid cores and/or the surroundingmaterial materials are derivatized or modified into siloxane functionalgroups, such as by reacting with an organotrihalosilane, e.g.,octadecyltrichlorosilane, or a halopolyorganosilane, e.g.,octadecyldimethylchlorosilane. Alternatively, the surface organic andsilanol groups of the hybrid cores and/or the surrounding materialmaterials are both derivatized or modified. The surface of thethus-prepared material is then covered by the organic groups, e.g.,alkyl, embedded during the gelation and the organic groups added duringthe derivatization process or processes. The surface coverage by theoverall organic groups is higher than in conventional silica-basedpacking materials and, therefore, the surface concentration of theremaining silanol groups in the hybrid particles is smaller. Theresulting material, used as a stationary phase for LC, shows excellentpeak shape for basic analytes and better stability to alkaline mobilephases than silica-based packing materials.

Where the prepolymerization step involves co-hydrolyzing a mixture ofthe two or more components in the presence of an acid catalyst, thecontent of the organoalkoxysilane, e.g., organotrialkoxysilane can bevaried, e.g., from about 0.03 to about 1.0 mole per mole, or morepreferably, about 0.2 to about 0.5 mole per mole, of thetetraalkoxysilane. The amount of the water used for the hydrolysis canbe varied, e.g., from 1.10 to 1.35 mole per mole of the silane. Thesilane, water and the ethanol mixture, in the form of a homogeneoussolution, is stirred and heated to reflux under a flow of argon. Afterit is refluxed for a time sufficient to prepolymerize to formpolyorganoalkoxysiloxane (POS), e.g., polyalkylalkoxysiloxane, thesolvent and the side product, mainly ethanol, is distilled off from thereaction mixture. Thereafter, the residue is heated at an elevatedtemperature, e.g., in the range of 45 to 85° C. under an atmosphere ofan inert gas, e.g., nitrogen, argon, etc., for a period of time, e.g.,0.5 to 48 h. The residue is further heated at 95° C. to 120° C., e.g.,for 1 to 3 h at atmospheric pressure or under reduced pressure, e.g.,10⁻²-10⁻³ torr, to remove any volatile species.

In the second step, the POS is suspended into fine beads in a solutioncontaining water and an alcohol, such as ethanol or butanol, at 55° C.by agitation. The volume percent of alcohol in the solution is variedfrom 10 to 20%. A surfactant such TRITON® X-100, TRITON® X-165, assodium dodecylsulfate (SDS), ammonia docecylsulfate or TRISdocecylsulfate, is added into the suspension as the suspending agent.The surfactants, are believed to be able to orient at thehydrophobic/hydrophilic interface between the POS beads and the aqueousphase to stabilize the POS beads. The surfactants are also believed toenhance the concentration of water and the base catalyst on the surfaceof the POS beads during the gelation step, through their hydrophilicgroups, which induces the gelling of the POS beads from the surfacetowards the center. Use of surfactants to modulate the surface structureof the POS beads stabilizes the shape of the POS beads throughout thegelling process and minimizes or suppresses formation of particleshaving an irregular shapes, e.g., “shell shaped”, and inhomogeneousmorphology.

It is also possible to suspend a solution containing POS and a porogenin the aqueous phase, instead of POS alone. The porogen, which isinsoluble in the aqueous phase, remains in the POS beads during thegelation step and functions as a porogen. Porogen include, e.g., tolueneand mesitylene. By controlling the relative amount of toluene in thePOS/toluene solution, the pore volume of the final hybrid particles canbe more precisely controlled. This allows the preparation of hybridparticles having large pore volume, e.g., 0.25-1.5 cm³/g.

The gelation step is initiated by adding the basic catalyst, e.g.,ammonium hydroxide into the POS suspension. Thereafter, the reactionmixture is agitated to drive the reaction to completion. Ammoniumhydroxide and sodium hydroxide are preferred. The particles are isolatedand washed with water. The condensation can be furthered by redispersingthe particles in an aqueous acid suspension at reflux for 1-4 days. Theuse of hydrochloric acid is preferred. The thus-prepared freshmadehybrid cores and/or surrounding material materials are filtered andwashed with water and methanol free of ammonium ions, then dried.

In one embodiment, the pore structure of the as-prepared hybrid coresand/or surrounding material materials is modified by hydrothermaltreatment, which enlarges the openings of the pores as well as the porediameters, as confirmed by nitrogen (N₂) sorption analysis. Thehydrothermal treatment is performed by preparing a slurry containing theas-prepared hybrid material and a solution of a base in water, heatingthe slurry in an autoclave at an elevated temperature, e.g., 100 to 200°C., for a period of 10 to 30 h. The use of an alkyl amine such astrimethylamine (TEA) or Tris(hydroxymethyl) methyl amine or the use ofsodium hydroxide is advantageous. The thus-treated hybrid material iscooled, filtered and washed with water and methanol, then dried at 80°C. under reduced pressure for 16 h.

In certain embodiments, following hydrothermal treatment, the surfacesof the hybrid cores and/or the materials are modified with variousagents. Such “surface modifiers” include (typically) organic functionalgroups which impart a certain chromatographic functionality to achromatographic stationary phase. The porous inorganic/organic hybridparticles possess both organic groups and silanol groups which mayadditionally be substituted or derivatized with a surface modifier.

The surface of the hydrothermally treated hybrid cores and/orsurrounding material materials contains organic groups, which can bederivatized by reacting with a reagent that is reactive towards theparticles' organic group. For example, vinyl groups on the particle canbe reacted with a variety of olefin reactive reagents such as bromine(Br₂), hydrogen (H₂), free radicals, propagating polymer radicalcenters, dienes and the like. In another example, hydroxyl groups on theparticle can be reacted with a variety of alcohol reactive reagents suchas isocyanates, carboxylic acids, carboxylic acid chlorides and reactiveorganosilanes as described below. Reactions of this type are well knownin the literature, see, e.g., March, J. Advanced Organic Chemistry,3^(rd) Edition, Wiley, New York, 1985; Odian, G. The Principles ofPolymerization, 2^(nd) Edition, Wiley, New York, 1981.

In addition, the surface of the hydrothermally treated hybrid coresand/or surrounding material materials also contains silanol groups,which can be derivatized by reacting with a reactive organosilane. Thesurface derivatization of the hybrid cores and/or surrounding materialmaterials is conducted according to standard methods, for example byreaction with octadecyltrichlorosilane or octadecyldimethylchlorosilanein an organic solvent under reflux conditions. An organic solvent suchas toluene is typically used for this reaction. An organic base such aspyridine or imidazole is added to the reaction mixture to catalyze thereaction. The product of this reaction is then washed with water,toluene and acetone and dried at 80° C. to 100° C. under reducedpressure for 16 h. The resultant hybrid particles can be further reactedwith a short-chain silane such as trimethylchlorosilane to endcap theremaining silanol groups, by using a similar procedure described above.

Surface modifiers such as disclosed herein are attached to the basematerial, e.g., via derivatization or coating and later crosslinking,imparting the chemical character of the surface modifier to the basematerial. In one embodiment, the organic groups of the hybrid coresand/or surrounding material materials react to form an organic covalentbond with a surface modifier. The modifiers can form an organic covalentbond to the particle's organic group via a number of mechanisms wellknown in organic and polymer chemistry including but not limited tonucleophilic, electrophilic, cycloaddition, free-radical, carbene,nitrene and carbocation reactions. Organic covalent bonds are defined toinvolve the formation of a covalent bond between the common elements oforganic chemistry including but not limited to hydrogen, boron, carbon,nitrogen, oxygen, silicon, phosphorus, sulfur and the halogens. Inaddition, carbon-silicon and carbon-oxygen-silicon bonds are defined asorganic covalent bonds, whereas silicon-oxygen-silicon bonds that arenot defined as organic covalent bonds.

The term “functionalizing group” includes organic functional groupswhich impart a certain chromatographic functionality to achromatographic stationary phase, including, e.g., octadecyl (C18) orphenyl. Such functionalizing groups are incorporated into base materialdirectly, or present in, e.g., surface modifiers such as disclosedherein which are attached to the base material, e.g., via derivatizationor coating and later crosslinking, imparting the chemical character ofthe surface modifier to the base material.

In certain embodiments, silanol groups are surface modified. In otherembodiments, organic groups are surface modified. In still otherembodiments, the hybrid cores' and/or surrounding material materials'organic groups and silanol groups are both surface modified orderivatized. In another embodiment, the particles are surface modifiedby coating with a polymer. In certain embodiments, surface modificationby coating with a polymer is used in conjunction with silanol groupmodification, organic group modification, or both silanol and organicgroup modification.

More generally, the surface of hybrid cores and/or surrounding materialmaterials may be modified by: treatment with surface modifiers includingcompounds of formula Z_(a)(R¹)_(b)Si—R″, where Z=Cl, Br, I, C₁-C₅alkoxy, dialkylamino, e.g., dimethylamino, or trifluoromethanesulfonate;a and b are each an integer from 0 to 3 provided that a+b=3; R′ is aC₁-C₆ straight, cyclic or branched alkyl group, and R″ is afunctionalizing group. In certain instances, such particles have beensurface modified by coating with a polymer.

R′ includes, e.g., methyl, ethyl, propyl, isopropyl, butyl, t-butyl,sec-butyl, pentyl, isopentyl, hexyl or cyclohexyl; preferably, R′ ismethyl.

The functionalizing group R″ may include alkyl, alkenyl, alkynyl, aryl,cyano, amino, diol, nitro, ester, cation or anion exchange groups, analkyl or aryl group containing an embedded polar functionalities orchiral moieties. Examples of suitable R″ functionalizing groups includechiral moieties, C₁-C₃₀ alkyl, including C₁-C₂₀, such as octyl (C₈),octadecyl (C₁₈) and triacontyl (C₃₀); alkaryl, e.g., C₁-C₄-phenyl;cyanoalkyl groups, e.g., cyanopropyl; diol groups, e.g., propyldiol;amino groups, e.g., aminopropyl; and alkyl or aryl groups with embeddedpolar functionalities, e.g., carbamate functionalities such as disclosedin U.S. Pat. No. 5,374,755, and chiral moieties. Such groups includethose of the general formula

wherein l, m, o, r and s are 0 or 1, n is 0, 1, 2 or 3 p is 0, 1, 2, 3or 4 and q is an integer from 0 to 19; R³ is selected from the groupconsisting of hydrogen, alkyl, cyano and phenyl; and Z, R′, a and b aredefined as above. Preferably, the carbamate functionality has thegeneral structure indicated below:

wherein R⁵ may be, e.g., cyanoalkyl, t-butyl, butyl, octyl, dodecyl,tetradecyl, octadecyl, or benzyl. Advantageously, R⁵ is octyl, dodecyl,or octadecyl.

In certain applications, such as chiral separations, the inclusion of achiral moiety as a functionalizing group is particularly advantageous.

Polymer coatings are known in the literature and may be providedgenerally by polymerization or polycondensation of physisorbed monomersonto the surface without chemical bonding of the polymer layer to thesupport (type I), polymerization or polycondensation of physisorbedmonomers onto the surface with chemical bonding of the polymer layer tothe support (type II), immobilization of physisorbed prepolymers to thesupport (type III) and chemisorption of presynthesized polymers onto thesurface of the support (type IV). see, e.g., Hanson, et al., J. Chromat.A656 (1993) 369-380, the text of which is incorporated herein byreference. As noted above, coating the hybrid material with a polymermay be used in conjunction with various surface modifications describedin the invention.

Thus, in certain embodiments, the surface modifier is selected from thegroup consisting of octyltrichlorosilane, octadecyltrichlorosilane,octyldimethylchlorosilane and octadecyldimethylchlorosilane. In afurther embodiment, the surface modifier is selected from the groupconsisting of octyltrichlorosilane and octadecyltrichlorosilane.

In another embodiment, the hybrid cores and/or surrounding materialmaterials have been surface modified by a combination of organic groupand silanol group modification.

In other embodiments, the hybrid cores and/or surrounding materialmaterials have been surface modified by a combination of organic groupmodification and coating with a polymer.

In other embodiments, the hybrid cores and/or surrounding materialmaterials have been surface modified by a combination of silanol groupmodification and coating with a polymer.

In another embodiment, the hybrid cores and/or surrounding materialmaterials have been surface modified via formation of an organiccovalent bond between the hybrid cores' and/or surrounding materialmaterials' organic group and the modifying reagent.

In certain embodiments, the hybrid cores and/or surrounding materialmaterials have been surface modified by a combination of organic groupmodification, silanol group modification and coating with a polymer.

In one embodiment, the hybrid cores and/or surrounding materialmaterials have been surface modified by silanol group modification.

In another embodiment, the invention provides a method wherein thehybrid cores and/or surrounding material materials are modified byfurther including a porogen. In a further embodiment, the porogen isselected from the group consisting of cyclohexanol, toluene, mesitylene,2-ethylhexanoic acid, dibutylphthalate, 1-methyl-2-pyrrolidinone,1-dodecanol and TRITON® X-45. In certain embodiments, the porogen istoluene or mesitylene.

In one embodiment, the invention provides a method wherein the hybridcores and/or surrounding material materials are further modified byincluding a surfactant or stabilizer. In certain embodiments, thesurfactant is TRITON® X-45, TRITON® X100, TRITON® X305, TLS, PLURONIC®F-87, PLURONIC® P-105, PLURONIC® P-123, sodium dodecylsulfate (SDS),ammonia docecylsulfate, TRIS docecylsulfate, or TRITON® X-165. Incertain embodiments, the surfactant is sodium dodecylsulfate (SDS),ammonia docecylsulfate, or TRIS docecylsulfate.

Certain embodiments of the synthesis of the hybrid cores and/orsurrounding material materials described above are further illustratedin the Examples below.

EXAMPLES

The present invention may be further illustrated by the followingnon-limiting examples describing the preparation of porousinorganic/organic hybrid particles and their use.

Materials

All reagents were used as received unless otherwise noted. Those skilledin the art will recognize that equivalents of the following supplies andsuppliers exist and, as such, the suppliers listed below are not to beconstrued as limiting.

Characterization

Those skilled in the art will recognize that equivalents of thefollowing instruments and suppliers exist and, as such, the instrumentslisted below are not to be construed as limiting.

The % C values were measured by combustion analysis (CE-440 ElementalAnalyzer; Exeter Analytical Inc., North Chelmsford, Mass.) or byCoulometric Carbon Analyzer (modules CM5300, CM5014, UIC Inc., Joliet,Ill.). The specific surface areas (SSA), specific pore volumes (SPV) andthe average pore diameters (APD) of these materials were measured usingthe multi-point N₂ sorption method (MICROMERITICS' ASAP 2400;MICROMERITICS™ Instruments Inc., Norcross, Ga.). The SSA was calculatedusing the BET method, the SPV was the single point value determined forP/P₀>0.98 and the APD was calculated from the desorption leg of theisotherm using the BJH method. The micropore surface area (MSA) wasdetermined as the cumulative adsorption pore diameter data for pores <34Å subtracted from the specific surface area (SSA). The median mesoporediameter (MPD) and mesopore pore volume (MPV) were measured by mercuryporosimetry (MICROMERITICS' AutoPore IV, MICROMERITICS™ InstrumentsInc., Norcross, Ga.). Skeletal densities were measured using aMICROMERITICS™ AccuPyc 1330 Helium Pycnometer (V2.04N, Norcross, Ga.).Scanning electron microscopic (SEM) image analyses were performed (JEOL™JSM-5600 instrument, Tokyo, Japan) at 7 kV. High resolution SEM imageanalyses were performed using a Focused Ion Beam (FIB/SEM) instrument(Helios 600 NANOLAB™, FEI Company, Hillsboro, Oreg.) at 20 kV. Particlesizes were measured using a BECKMAN COULTER™ Multisizer 3 analyzer(30-μm aperture, 70,000 counts; Miami, Fla.). The particle diameter (dp)was measured as the 50% cumulative diameter of the volume based particlesize distribution. The width of the distribution was measured as the 90%cumulative volume diameter divided by the 10% cumulative volume diameter(denoted 90/10 ratio). Viscosity was determined for these materialsusing a Brookfield digital viscometer Model DV-II (Middleboro, Mass.).FT-IR spectra were obtained using a BRUKER™ Optics Tensor 27 (Ettlingen,Germany). Multinuclear (¹³C, ²⁹Si) CP-MAS NMR spectra were obtainedusing a BRUKER™ Instruments Avance-300 spectrometer (7 mm doublebroadband probe). The spinning speed was typically 5.0-6.5 kHz, recycledelay was 5 sec. and the cross-polarization contact time was 6 msec.Reported ¹³C and ²⁹Si CP-MAS NMR spectral shifts were recorded relativeto tetramethylsilane using the external standards adamantane (¹³C CP-MASNMR, □ 38.55) and hexamethylcyclotrisiloxane (²⁹Si CP-MAS NMR, □ −9.62).Populations of different silicon environments were evaluated by spectraldeconvolution using DMFit software. [Massiot, D.; Fayon, F.; Capron, M.;King, I.; Le Calvé, S.; Alonso, B.; Durand, J.-O.; Bujoli, B.; Gan, Z.;Hoatson, G. Magn. Reson. Chem. 2002, 40, 70-76]

Example 1 Synthesis of Polyorganosiloxanes

One or more tetraalkoxysilanes or organoalkoxysilanes (all from GELEST™Inc., Morrisville, Pa. or United Chemical Technologies, INC., Bristol,Pa.) or zirconium n-propoxide (70% in propanol, GELEST™ Inc.,Morrisville, Pa., 172.5 g solution used in reaction 1n) were mixed withethanol (anhydrous, J.T. BAKER™, Phillipsburgh, N.J.) and an aqueoushydrochloric acid solution (ALDRICH™, Milwaukee, Wis.) in a flask.Reactions 1a-1r, 1u-1y used 0.1 N HCl, reactions is and 1t used 0.01 NHCl, reaction 1z used 0.1 M acetic acid (J.T. BAKER™). Hydroquinone(ALDRICH™, Milwaukee, Wis.) was also added to reaction 1o (8.4 mg) andreaction 1p (17.6 mg) to prevent polymerization of themethacryloxypropyl groups. Product 1y was prepared following aliterature protocol (as described in K. Unger, et. Al. Colloid & PolymerScience vol. 253 pp. 658-664 (1975)). The resulting solution wasagitated and refluxed for 16 hours in an atmosphere of argon ornitrogen. Alcohol was removed from the flask by distillation atatmospheric pressure. Residual alcohol and volatile species were removedby heating at 95-120° C. for 1-2 hours in a sweeping stream of argon ornitrogen. The resulting polyorganoalkoxy siloxanes were clear viscousliquids. The chemical formulas are listed in Table 1 for theorganoalkoxysilanes used to make the product polyorganoalkoxysiloxanes(POS). Specific amounts are listed in Table 2 for the starting materialsused to prepare products 1a-1x. Structural analysis was performed usingNMR spectroscopy.

TABLE 1 Chemical Formula Chemical Formula Chemical Formula Mol RatioProduct A B C A:B:C 1a CH₂═C(CH₃)CO₂(CH₂)₃Si(OCH₃)₃ Si(OCH₂CH₃)₄ — 1:5:01b (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ Si(OCH₂CH₃)₄ — 3:1:0 1c(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ Si(OCH₂CH₃)₄ — 1:4:0 1d CH₃Si(OCH₂CH₃)₃Si(OCH₂CH₃)₄ — 1:2:0 1e (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃CH₃(CH₂)₁₇Si(OCH₃)₃ — 20:1:0 1f (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ — — 1:0:01g (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ CH₃(CN)CH(CH₂)₂Si(OCH₂CH₃)₃ — 10:1 1h(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ (CH₃CH₂)₂Si(OCH₂CH₃)₂ — 10:1 1i(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ CH₂═CHC(O)N[(CH₂)₃Si(OCH₃)]₂ — 20:1 1j(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ CF₃(CF₂)₅(CH₂)₂Si(OCH₂CH₃)₃ — 10:1 1k(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ Si(OCH₂CH₃)₄ CH₂═C(CH₃)CO₂(CH₂)₃Si(OCH₃)₃0.3:2.4:0.7 1l (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ Si(OCH₂CH₃)₄(CH₃)₃COC(O)NH(CH₂)₃Si(OCH₂CH₃)₃ 0.3:2.7:0.7 1m(CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ Si(OCH₂CH₃)₄ C₆H₅(CH₂)₂Si(OCH₃)₃0.3:2.4:0.7 1n (CH₃CH₂O)₃Si(CH₂)₂Si(OCH₂CH₃)₃ Si(OCH₂CH₃)₄Zr(O(CH₂)₂CH₃)₄ 1:3:0.2 1o CH₂═C(CH₃)CO₂(CH₂)₃Si(OCH₃)₃ — — 1:0:0 1pSi(OCH₂CH₃)₄ CH₂═C(CH₃)CO₂(CH₂)₃Si(OCH₃)₃ — 1:1:0 1q Si(OCH₂CH₃)₄(CH₃)₃COC(O)NH(CH₂)₃Si(OCH₂CH₃)₃ — 1:1:0 1r(CH₃)₃COC(O)NH(CH₂)₃Si(OCH₂CH₃)₃ — — 1:0:0 1s Si(OCH₂CH₃)₄CH₃CO₂(CH₂)₃Si(OCH₃)₃ — 1:1:0 1t CH₃CO₂(CH₂)₃Si(OCH₃)₃ — — 1:0:0 1uSi(OCH₂CH₃)₄ C₆F₅Si(OCH₂CH₃)₃ — 5:1:0 1v Si(OCH₂CH₃)₄ CH₃(CH₂)₃Si(OCH₃)₃— 1:1:0 1w CH₃(CH₂)₃Si(OCH₃)₃ — — 1:0:0 1x Si(OCH₂CH₃)₄(CH₃CH₂)₂Si(OCH₂CH₃)₂ 1:1:0 1y Si(OCH₂CH₃)₄ — — 1:0:0 1zCH₃CO₂(CH₂)₃Si(OCH₃)₃ — — 1:0:0

TABLE 2 1a 62 260 0 35 218 35.5 40 1b 399 78 0 41 218 36.9 50 1c 106 2500 40 218 31.6 84 1d 534 1248 0 203 450 31.1 36 1e 507 27 0 44 179 39.883 1f 519 0 0 134 653 34.7 70 1g 484 34 0 31 179 37.0 63 1h 484 24 0 42218 36.5 53 1i 507 28 0 45 218 38.5 200 1j 338 49 0 30 125 35.9 74 1k 47221 77 37 218 36.2 64 1l 43 228 91 34 218 37.4 77 1m 47 229 70 37 21839.8 45 1n 654 1,152 121 204 921 31.9 67 1o 373 0 0 22 218 49.1 21 1p156 186 0 26 218 44.2 19 1q 156 241 0 26 218 42.7 256 1r 482 0 0 22 21848.8 701 1s 156 167 0 26 218 38.7 34 1t 333 0 0 22 218 42.4 104 1u 14947 0 16 125 35.6 12 1v 156 133 0 26 218 43.5 6 1w 267 0 0 22 218 48.1 91x 156 132 0 22 218 40.9 7 1z 667 0 0 46 357 42.3 104

Example 2 Hybrid Inorganic/Organic Material Surrounding of HybridParticles

To a suspension of 5 μm BEH porous hybrid particles (20 g, WatersCorporation, Milford, Mass.; 6.5% C; SSA=190 m²/g; SPV=0.80 cm³/g;APD=155 Å) of the formula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (preparedfollowing the method described in U.S. Pat. No. 6,686,035) in ethanol(anhydrous, J.T.-BAKER™, Phillipsburgh, N.J.; 5 mL/g) was added POS 1afrom Example 1. The solvent was slowly removed under reduced pressure ina rotary evaporator for 0.54 hours. The particles were isolated on 0.5μm filtration paper and washed repeatedly using ethanol (anhydrous,J.T.-BAKER™, Phillipsburgh, N.J.). The material was then heated 50° C.in a suspension with ethanol (3 mL/g, anhydrous, J.T.-BAKER™,Phillipsburgh, N.J.), deionized water (7 mL/g) and 30% ammoniumhydroxide (20 g; J.T. BAKER™, Phillipsburgh, N.J.) for 20 hours. Thereaction was then cooled and the product was filtered and washedsuccessively with water and methanol (J.T. BAKER™, Phillipsburgh, N.J.).The product was then dried at 80° C. under reduced pressure for 16hours. Specific amounts of starting materials used to prepare theseproducts are listed in Table 3. The % C values, specific surface areas(SSA), specific pore volumes (SPV) and average pore diameters (APD) ofthese materials are listed in Table 3.

TABLE 3 Evaporation POS Time SSA SPV APD Product (g) (h) % C (m²/g)(cm³/g) (Å) 2a 1.54 0.5 6.65 191 0.80 153 2b 16.42 1 6.61 187 0.66 1412c 56.19 4 7.05 190 0.80 154

Example 3 Hybrid Inorganic/Organic Material Surrounding of HybridParticles

To a suspension of 5 μm BEH porous hybrid particles (20 g, WatersCorporation, Milford, Mass.; 6.5% C; SSA=190 m²/g; SPV=0.80 cm³/g;APD=155 Å) of the formula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (preparedfollowing the method described in U.S. Pat. No. 6,686,035) in drytoluene (FISHER SCIENTIFIC™, Fairlawn, N.J.; 5 mL/g) was added POS 1afrom Example 1 and water. This reaction was heated at 80° C. for onehour and 110° C. for 20 hours using a Dean-Stark trap to remove residualwater. The reaction was cooled to room temperature and particles wereisolated on 0.5 μm filtration paper and washed repeatedly using ethanol(anhydrous, J.T.-BAKER™, Phillipsburgh, N.J.). The material was thenheated to 50° C. in a suspension with ethanol (3 mL/g, anhydrous,J.T.-BAKER™, Phillipsburgh, N.J.), deionized water (7 mL/g) and 30%ammonium hydroxide (20 g; J.T. Baker, Phillipsburgh, N.J.) for 4 hours.The reaction was then cooled and the product was filtered and washedsuccessively with water and methanol (Fisher Scientific, Fairlawn,N.J.). The product was then dried at 80° C. under reduced pressure for16 hours. Specific amounts of starting materials used to prepare theseproducts are listed in Table 4. The % C values, specific surface areas(SSA), specific pore volumes (SPV), average pore diameters (APD), andchanges in SPV (ΔSPV) are listed in Table 4.

The increase in carbon content (1.0-1.8% C) and reduction in SPV (0.10cm³/g average change) were observed by this approach. SEM analysisindicated equivalent particle morphology and surface features of thestarting particles. Particle size analysis (by COULTER COUNTER™, CoulterElectronics, Inc. Illinois) indicated equivalent particle size anddistribution of the starting particles. This suggests the decreasedporosity of this Material Surrounding process is due to a filling of theporous particle framework, and is not due to the introduction of surfacedebris or a secondary nonporous particle distribution. The reduction inAPD also indicates that this Material Surrounding process is filling thepore framework. The slight increase in SSA may indicate the surroundingmaterial has a small degree of porosity.

TABLE 4 Particles POS Water SSA SPV APD ΔSPV Product (g) (g) (mL) % C(m²/g) (cm³/g) (Å) (cm³/g) 3a 20 16.42 0.4 7.67 199 0.68 137 −0.12 3b 2016.42 0.8 7.71 198 0.68 137 −0.12 3c 7.0 7.92 0.0 8.06 217 0.66 124−0.14 3d 7.0 7.92 0.2 7.50 194 0.67 137 −0.13 3e 7.0 7.92 0.4 8.25 2290.61 118 −0.19

Example 4 Hybrid Inorganic/Organic Material Surrounding of HybridParticles

To a suspension of 3.5 μm BEH porous hybrid particles (WatersCorporation, Milford, Mass.; 6.5% C; SSA=185 m²/g; SPV=0.76 cm³/g;APD=146 Å) of the formula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (preparedfollowing the method described in U.S. Pat. No. 6,686,035) in drytoluene (FISHER SCIENTIFIC™, Fairlawn, N.J.; 5 mL/g for 4a-4b; 10 mL/gfor 4e-4i) was added POS 1a from Example 1 and water. This reaction washeated at 80° C. for one hour and 110° C. for 20 hours. Reactions 4a and4c did not employ the use of a Dean-Stark trap to remove residual water;while the other reactions used of a Dean-Stark trap. The reaction wascooled to room temperature and particles were isolated on 0.5 μmfiltration paper and washed repeatedly using ethanol (anhydrous,J.T.-BAKER™, Phillipsburgh, N.J.). The material was then heated 50° C.in a suspension with ethanol (3 mL/g, anhydrous, J.T.-BAKER™,Phillipsburgh, N.J.), deionized water (7 mL/g) and 30% ammoniumhydroxide (20 g; J.T. BAKER™, Phillipsburgh, N.J.) for 4 hours. Thereaction was then cooled and the product was filtered and washedsuccessively with water and methanol (FISHER SCIENTIFIC™, Fairlawn,N.J.). The product was then dried at 80° C. under reduced pressure for16 hours. Specific amounts of starting materials used to prepare theseproducts are listed in Table 5. The % C values, specific surface areas(SSA), specific pore volumes (SPV), average pore diameters (APD) andchanges in SPV (ASSA) are listed in Table 5.

Increases in carbon content (1.0-2.6% C) and reductions in SPV(0.12-0.44 cm³/g) were achieved by this Material Surrounding approach.SEM analysis confirmed equivalent particle morphology and surfacefeatures of the starting particles. Particle size analysis (by COULTERCOUNTER™, Coulter Electronics, Inc. Illinois) indicated equivalentparticle size and distribution of the starting particles. This suggeststhe decreased porosity of this Material Surrounding process is due to afilling of the porous particle framework, and is not due to theintroduction of surface debris or a secondary nonporous particledistribution.

TABLE 5 Particles POS Water SSA SPV APD ΔSPV Product (g) (g) (mL) % C(m²/g) (cm³/g) (Å) (cm³/g) 4a 20 32.84 1.6 7.70 201 0.58 119 −0.18 4b 2032.84 1.6 7.62 199 0.60 123 −0.16 4c 20 56.19 2.8 8.44 178 0.41 100−0.35 4d 20 56.19 2.8 8.06 183 0.50 114 −0.26 4e 20 100 5.0 8.92 2090.32 76 −0.44 4f 20 50 2.5 9.11 208 0.32 77 −0.44 4g 20 16.42 0.8 7.525193 0.64 133 −0.12 4h 50 41.05 0.8 7.49 200 0.64 131 −0.12

Example 5 Hydrothermal Processing of Hybrid Surrounded Hybrid Particles

As a means to modify the pore structure of surrounded hybrid particles,particles from Examples 3 and 4 were mixed with an aqueous solution of0.3 M tris(hydroxymethyl)aminomethane (TRIS, ALDRICH™ Chemical,Milwaukee, Wis.) at a slurry concentration of 5 mL/g. The pH of theresultant slurry was adjusted to 9.8 using acetic acid (J.T. BAKER™,Phillipsburgh, N.J.). The slurry was then enclosed in a stainless steelautoclave and heated to 155° C. for 20 hours. After cooling theautoclave to room temperature, the product was isolated on 0.5 μmfiltration paper and washed with water and methanol (FISHER SCIENTIFIC™,Suwanee, Ga.). The particles were then dried at 80° C. under vacuum for16 hours. Specific characterization data for these materials are listedin Table 6. Changes in product % C (Δ % C), SSA (ASSA) and APD (ΔAPD),relative to the precursor material from Examples 3 and 4, are listed inTable 6.

This set of experiments showed that hydrothermal processing ofsurrounded hybrid particles could be used to modify the pore attributesof these materials. All products had noticeable reductions in SSA,increases in APD and no significant changes in SPV or particlemorphology (as determined by SEM), when compared with the precursormaterials from Examples 3 and 4. It was concluded that the use ofhydrothermal treatment was successful in increasing the APD. The APD forthese products was within a range that is comparable with commerciallyavailable HPLC packing materials. Reductions in % C for these productsare due in part to a removal of surface alkoxides and the partialhydrolysis of the methacryloxypropyl group of the surrounding material.This hydrolysis results in the formation of a hydroxypropyl group (e.g.,HO(CH₂)₃SiO_(1.5)), as confirmed by NMR and FT-IR spectroscopy.

TABLE 6 SSA SPV APD ΔSSA ΔAPD Product Precursor % C (m²/g) (cm³/g) (Å) Δ% C (m²/g) (Å) 5a 3a, 3b 6.77 158 0.69 153 −0.92 −41 16 5b 4a 6.95 1580.61 140 −0.75 −43 21 5c 4b 6.96 159 0.63 142 −0.66 −40 19 5d 4c 6.95129 0.46 125 −1.49 −49 25 5e 4d 6.94 143 0.54 132 −1.12 −40 18 5f 4e6.86 116 0.36 113 −2.06 −93 37 5g 4f 7.01 119 0.37 112 −2.10 −89 35 5h4g 6.98 160 0.66 145 −0.55 −33 12 5i 4h 7.21 157 0.66 148 −0.28 −43 17

Example 6 Secondary Hybrid Inorganic/Organic Material Surrounding ofHybrid Particles

To a suspension of porous hybrid particles from Example 5 in dry toluene(FISHER SCIENTIFIC™, Fairlawn, N.J.; 10 mL/g) was added POS 1a fromExample 1 and water. This reaction was heated at 80° C. for one hour and110° C. for 20 hours using a Dean-Stark trap to remove residual water.The reaction was cooled to room temperature and particles were isolatedon 0.5 μm filtration paper and washed repeatedly using ethanol(anhydrous, J.T.-BAKER™, Phillipsburgh, N.J.). The material was thenheated to 50° C. in a suspension with ethanol (3 mL/g, anhydrous,J.T.-BAKER™, Phillipsburgh, N.J.), deionized water (7 mL/g) and 30%ammonium hydroxide (20 g; J.T. BAKER™, Phillipsburgh, N.J.) for 4 hours.The reaction was then cooled and the product was filtered and washedsuccessively with water and methanol (FISHER SCIENTIFIC™, Fairlawn,N.J.). The product was then dried at 80° C. under reduced pressure for16 hours. Specific amounts of starting materials used to prepare theseproducts are listed in Table 7. The % C values, specific surface areas(SSA), specific pore volumes (SPV), average pore diameters (APD), andchanges in SPV (ΔSPV) are listed in Table 7.

This set of experiments showed that repeated Material Surrounding can beused to further change the pore properties of these materials. Increasesin carbon content (0.7% C) and reduction in SPV (0.13 cm³/g) wereachieved with this Material Surrounding approach. Comparing theseproducts with the unmodified BEH particle used in Example 3 and 4, weobserve a larger increase in carbon content (1.00-1.36% C) and adecrease in SPV (0.23-0.24 cm³/g) have been achieved by this iterativeprocess. SEM analysis confirmed equivalent particle morphology andsurface features of the precursor materials.

TABLE 7 Water SSA SPV APD ΔSPV Product Precursor Particles (g) POS (g)(mL) % C (m²/g) (cm³/g) (Å) (cm³/g) 6a 5a 15 16.42 0.8 7.50 175 0.56 129−0.13 6b 5i 20 16.42 8 7.86 172 0.53 120 −0.13

Example 7 Hydrothermal Processing of Hybrid Inorganic/Organic SurroundedHybrid Particles

Hybrid particles from Examples 6 were mixed with an aqueous solution of0.3 M tris(hydroxymethyl)aminomethane (TRIS, ALDRICH™ Chemical,Milwaukee, Wis.) at a slurry concentration of 5 mL/g. The pH of theresultant slurry was adjusted to 9.8 using acetic acid (J.T. BAKER™,Phillipsburgh, N.J.). The slurry was then enclosed in a stainless steelautoclave and heated to 155° C. for 20 hours. After cooling theautoclave to room temperature, the products were isolated on 0.5 μmfiltration paper and washed with water and methanol (FISHER SCIENTIFIC™,Suwanee, Ga.). The particles were then dried at 80° C. under vacuum for16 hours. Specific characterization data for these materials are listedin Table 8. Changes in product % C (Δ % C), SSA (ASSA) and APD (ΔAPD),relative to the precursor material from Example 6, are listed in Table8.

This set of experiments showed that hydrothermal processing of repeatedsurrounded hybrid particles could be used reduce the SSA, increase APDand have no significant changes in SPV or particle morphology (asdetermined by SEM), when compared with the precursor materials.Reductions in % C for these products are due in part to a removal ofsurface alkoxides of the precursor materials and the partial hydrolysisof the methacryloxypropyl group of the surrounding material. Thishydrolysis results in the formation of a hydroxypropyl group (e.g.,HO(CH₂)₃SiO_(1.5)), as confirmed by NMR and FT-IR spectroscopy.

TABLE 8 SSA SPV APD ΔSSA ΔAPD Product Precursor % C (m²/g) (cm³/g) (Å) Δ% C (m²/g) (Å) 7a 6a 6.93 146 0.58 144 −0.57 −29 15 7b 6b 7.35 142 0.54138 −0.51 −30 18

Example 8 Hybrid Inorganic/Organic Material Surrounding of HybridParticles

To a suspension of 3.0-3.5 μm BEH porous hybrid particles (20 g, WatersCorporation, Milford, Mass.; 6.5% C; SSA=185-191 m²/g; SPV=0.76-0.82cm³/g; APD=146-153 Å) of the formula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄(prepared following the method described in U.S. Pat. No. 6,686,035) intoluene (FISHER SCIENTIFIC™, Fairlawn, N.J.; 10 ml/g) was added a POSfrom Example 1 (16.42 g) and deionized water (0.8 mL). Reactions 8u, 8vand 8ad used a 4.8 μm BEH porous particle. Reactions 8p and 8q used 8.2mL of deionized water. Reactions 8s and 8t were performed at a two-foldincreased scale, reactions 8w and 8x at ten-fold increased scale, andreaction 8y at 25-fold increased scale. Hydroquinone (30 ppm, ALDRICH™,Milwaukee, Wis.) was added to reactions 8n and 8o to preventpolymerization of the methacryloxypropyl group. Reactions were heated at80° C. for one hour and 110° C. for 20 hours using a Dean-Stark trap toremove residual water. The reaction was cooled to room temperature andparticles were isolated on 0.5 μm filtration paper and washed repeatedlyusing ethanol (anhydrous, J.T.-BAKER™, Phillipsburgh, N.J.). Thematerial was then heated 50° C. in a suspension with ethanol (3 mL/g,anhydrous, J.T.-BAKER™, Phillipsburgh, N.J.), deionized water (7 mL/g)and 30% ammonium hydroxide (20 g; J.T. BAKER™, Phillipsburgh, N.J.) for4 hours. The reaction was then cooled and the product was filtered andwashed successively with water and methanol (FISHER SCIENTIFIC™,Fairlawn, N.J.). The product was then dried at 80° C. under reducedpressure for 16 hours. The % C values, specific surface areas (SSA),specific pore volumes (SPV) and average pore diameters (APD) of thesematerials are listed in Table 9. Changes in product % C (Δ % C), and SPV(ΔSPV) are listed in Table 9.

This set of experiments showed that a variety of different POS can beused to create hybrid surrounded materials. This series of surroundedmaterials differ in hydrophobicity and surface activity. For example,the octadecyl groups of surrounded product 8d and partially fluorinatedgroups of surrounded product 8i may result in increased hydrophobicityover the unmodified BEH particles. The zirconium containing product 8mmay display increased surface activity, which may be beneficial for somechromatographic separations. The hydrophobic and strong electronwithdrawing nature of the perfluorophenyl containing surrounded product8t may display both increased hydrophobicity and modified surfacesilanol activity. As shown with product 8b, the use of a POS with theformula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ resulted in hybrid surroundedparticles that have the sample chemical composition as the unmodifiedparticles, allowing for changes only in particle pore properties.

Carbon content varied due to the composition of the surroundingmaterial. For example, product 8b showed no change in carbon content.This was expected since the surrounding material and the base particlehave the same chemical composition. The surrounding material of product8t, which has a lower carbon content than the BEH material, resulted ina reduction in carbon content of the surrounded product. Products 8u-8ywere repeat experiments aimed at determining the reproducibility of thisprocess at increased reaction scale. These products have goodreproducibility, having relative standard deviations less than 4.5% for% C, SSA, SPV, and APD data.

Reductions in SPV (−0.04 to −0.25 cm³/g) were also achieved by thisMaterial Surrounding approach. SEM analysis confirmed equivalentparticle morphology and surface features of the starting particles.Particle size analysis (by COULTER COUNTER™, Coulter Electronics, Inc.Illinois) indicated equivalent particle size and distribution to that ofthe starting particles.

TABLE 9 SSA SPV APD ΔSPV Product POS % C (m²/g) (cm³/g) (Å) Δ % C(cm³/g) 8a 1b 7.54 220 0.62 129 1.03 −0.14 8b 1c 6.51 197 0.63 138 0.00−0.13 8c 1d 6.44 179 0.67 142 −0.07 −0.09 8d 1e 7.46 205 0.68 143 0.95−0.08 8e 1f 7.36 210 0.67 136 0.85 −0.09 8f 1g 6.96 191 0.72 145 0.45−0.04 8g 1h 7.18 203 0.69 143 0.67 −0.07 8h 1i 7.91 226 0.65 121 1.40−0.11 8i 1j 7.21 203 0.69 145 0.70 −0.07 8j 1k 7.63 194 0.63 131 1.12−0.13 8k 1l 8.67 183 0.51 108 2.16 −0.25 8l 1m 7.42 197 0.67 136 0.91−0.09 8m 1n 6.70 267 0.54 86 0.19 −0.22 8n 1o 9.65 179 0.67 135 3.13−0.15 8o 1p 8.46 188 0.68 138 1.94 −0.14 8p 1q 10.78 157 0.53 125 4.26−0.25 8q 1r 11.06 150 0.60 130 4.54 −0.18 8r 1s 8.08 178 0.65 138 1.56−0.13 8s 1t 9.08 174 0.66 139 2.56 −0.12 8t 1u 6.22 189 0.71 149 −0.30−0.07 8u 1t 8.92 173 0.65 135 2.02 −0.14 8v 1t 8.93 174 0.65 135 2.03−0.14 8w 1t 9.01 171 0.60 128 2.36 −0.12 8x 1t 9.03 172 0.60 129 2.25−0.12 8y 1t 8.97 175 0.61 129 2.43 −0.11 8z 1z 9.08 171 0.60 126 2.54−0.12 8aa 1z 8.90 170 0.64 138 1.69 −0.12 8ab 1z 8.83 172 0.65 136 1.62−0.11 8ac 1z 8.82 167 0.62 137 2.13 −0.13 8ad 1z 8.90 166 0.62 134 2.09−0.12

Example 9 Hydrothermal Processing of Hybrid Coated Hybrid Particles

Hybrid particles from Examples 8 were mixed with an aqueous solution of0.3 M tris(hydroxymethyl)aminomethane (TRIS, ALDRICH™ Chemical,Milwaukee, Wis.) at a slurry concentration of 5 mL/g. The pH of theresultant slurry was adjusted to 9.8 using acetic acid (J.T. BAKER™,Phillipsburgh, N.J.). The slurry was then enclosed in a stainless steelautoclave and heated to 155° C. for 20 hours. After cooling theautoclave to room temperature, the product was isolated on 0.5 μmfiltration paper and washed with water and methanol (FISHER SCIENTIFIC™,Suwanee, Ga.). The particles were then dried at 80° C. under vacuum for16 hours. Specific characterization data for these materials are listedin Table 10.

This set of experiments showed that hydrothermal processing ofsurrounded hybrid particles could be used reduce the SSA, increase APDand have no significant changes in SPV or particle morphology (asdetermined by SEM), when compared with the precursor materials. Whilemost modifications in % C were small (<0.35% C), larger reductions in %C for some of these products are due in part to a removal of surfacealkoxides of the precursor materials and chemical modification of someof specific organofunctional groups of the surrounding material. Forexample, the partial ester hydrolysis for products 9j, 9n, 9o, 9r and 9sresults in the formation of a hydroxypropyl group (e.g.,HO(CH₂)₃SiO_(1.5)). The deprotection of the tert-butoxycarbonyl groupfor products 9k, 9p and 9q results in the formation of an aminopropylgre.g., e.g., NH₂(CH₂)₃SiO_(1.5)), as confirmed by NMR spectroscopy.

The modifications in pore structure obtained by hydrothermal treatmentof a surrounded hybrid particle can be observed in the nitrogendesorption data (BJH dV/dlog(D) pore volume data). As shown in FIG. 1for the Material Surrounding and hydrothermal treatment products 8b and9b, respectively, noticeable changes in mean pore diameter are obtainedby this process. The width of the pores size distribution decreasedrelative to the unmodified BEH hybrid particles as a result of thisprocess. Repeat experiments, products 9u-9y, demonstrate goodreproducibility with relative standard deviations for % C, SSA, SPV, andAPD less than 4.5%.

TABLE 10 SSA SPV APD ΔSSA ΔAPD Product Precursor % C (m²/g) (cm³/g) (Å)Δ % C (m²/g) (Å) 9a 8a 7.30 145 0.64 158 −0.24 −75 29 9b 8b 6.40 1250.64 180 −0.11 −72 42 9c 8c 6.37 142 0.67 164 −0.07 −37 22 9d 8d 7.29147 0.67 163 −0.17 −58 20 9e 8e 7.20 148 0.66 162 −0.16 −62 26 9f 8f6.82 155 0.71 167 −0.14 −36 22 9g 8g 7.08 150 0.69 163 −0.10 −53 20 9h8h 7.76 156 0.64 145 −0.15 −70 24 9i 8i 7.23 151 0.69 165 0.02 −52 20 9j8j 7.15 157 0.65 149 −0.48 −37 18 9k 8k 7.13 122 0.57 158 −1.54 −61 509l 8l 7.14 156 0.67 154 −0.28 −41 18 9m 8m 6.88 152 0.54 129 0.18 −11543 9n 8n 8.14 176 0.71 144 −1.52 −3 9 9o 8o 7.48 170 0.7 149 −0.98 −1811 9p 8p 7.94 142 0.63 155 −2.84 −15 30 9q 8q 8.43 149 0.68 163 −2.64 −133 9r 8r 7.83 162 0.67 147 −0.25 −16 9 9s 8s 8.52 161 0.67 145 −0.56 −136 9t 8t 6.05 134 0.71 189 −0.17 −55 40 9u 8u 8.53 165 0.67 140 −0.39 −85 9v 8v 8.63 164 0.66 140 −0.30 −10 5 9w 8w 8.61 164 0.62 134 −0.40 −7 69x 8x 8.54 162 0.62 133 −0.49 −10 4 9y 8y 8.59 161 0.61 134 −0.38 −14 59z 8z 8.63 165 0.62 133 −0.45 −6 7 9aa 8aa 8.42 160 0.66 141 −0.48 −10 39ab 8ab 8.51 162 0.66 141 −0.32 −10 5 9ac 8ac 8.36 159 0.65 142 −0.46 −85 9ad 8ad 8.44 162 0.65 140 −0.46 −4 6

Example 10 Silica Based Material Surrounding of Hybrid Particles

To a suspension of 3.5 μm BEH porous hybrid particles (WatersCorporation, Milford, Mass.; 6.5% C; SSA=185 m²/g; SPV=0.76 cm³/g;APD=146 Å) of the formula (Q_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (preparedfollowing the method described in U.S. Pat. No. 6,686,035) in drytoluene (FISHER SCIENTIFIC™, Fairlawn, N.J.; 10 mL/g) was added POS 1yfrom Example 1 and deionized water. This reaction was heated at 80° C.for one hour and 110° C. for 20 hours using a Dean-Stark trap to removeresidual water. The reaction was cooled to room temperature andparticles were isolated on 0.5 μm filtration paper and washed repeatedlyusing ethanol (anhydrous, J.T. BAKER™, Phillipsburgh, N.J.). Thematerial was then heated 50° C. in a suspension with ethanol (3 mL/g,anhydrous, J.T.-BAKER™, Phillipsburgh, N.J.), deionized water (7 ml/g)and 30% ammonium hydroxide (20 g; J.T. BAKER™, Phillipsburgh, N.J.) for4 hours. The reaction was then cooled and the product was filtered andwashed successively with water and methanol (FISHER SCIENTIFIC™,Fairlawn, N.J.). The product was then dried at 80° C. under reducedpressure for 16 hours. Specific amounts of starting materials used toprepare these products are listed in Table 11. The % C values, specificsurface areas (SSA), specific pore volumes (SPV) and average porediameters (APD) of these materials are listed in Table 11. Changes inproduct % C (Δ % C) and SPV (ΔSPV) are listed in Table 11.

This set of experiments showed that a tetraalkoxysilane-based POS can beused to create silica surrounded hybrid materials. This may allow formodification of particle surface properties (e.g., silanol activity andhydrophilicity). Carbon content, SSA, SPV and APD decreased as a resultof silica Material Surrounding of these hybrid materials, which is dueto the lack of carbon in the surrounding material (e.g., SiO₂). SEManalysis confirmed equivalent particle morphology and surface featuresof the starting particles. Particle size analysis (by COULTER COUNTER™,Coulter Electronics, Inc. Illinois) indicated equivalent particle sizeand distribution of the starting particles.

TABLE 11 Particles POS Water SSA SPV APD ΔSPV Product (g) (g) (mL) % C(m²/g) (cm³/g) (Å) Δ % C (cm³/g) 10a 50 41.05 2.1 6.29 173 0.63 140−0.23 −0.13 10b 20 16.42 0.8 5.94 182 0.64 141 −0.57 −0.12

Example 11 Hydrothermal Processing of Silica Coated Hybrid Particles

Hybrid particles from Example 10 were mixed with an aqueous solution of0.3 M tris(hydroxymethyl)aminomethane (TRIS, ALDRICH™ Chemical,Milwaukee, Wis.) at a slurry concentration of 5 mL/g. The pH of theresultant slurry was adjusted to 9.8 using acetic acid (J.T. BAKER™,Phillipsburgh, N.J.). The slurry was then enclosed in a stainless steelautoclave and heated to 155° C. for 20 hours. After cooling theautoclave to room temperature, the product was isolated on 0.5 μmfiltration paper and washed with water and methanol (FISHER SCIENTIFIC™,Suwanee, Ga.). The particles were then dried at 80° C. under vacuum for16 hours. Specific characterization data for these materials are listedin Table 12.

This set of experiments showed that hydrothermal processing of silicasurrounded hybrid particles could be used reduce the SSA, increase APDand have no significant changes in % C, SPV or particle morphology (asdetermined by SEM) when compared with the precursor materials.

TABLE 12 SSA SPV APD ΔSSA ΔAPD Product Precursor % C (m²/g) (cm³/g) (Å)(m²/g) (Å) 11a 10a 6.01 123 0.64 184 −50 44 11b 10b 5.80 129 0.65 178−53 37

Example 12 Addition of Nanoparticles to Polyorganosiloxanes

Diamond nanoparticles (Nanostructured & Amorphous Materials, Inc,Houston, Tex., 4-25 nm) or silicon carbide nanoparticles(-SIGMA-ALDRICH™, Saint Louis, Mo., <100 nm) were added to POS 1c inExample 1 to yield a 0.1-0.2 wt % dispersion. Dispersion was achievedusing a rotor/stator mixer (Mega Sheer, Charles Ross & Son Co.,Hauppauge, N.Y.). Products were then centrifuged (Thermo EXD, 4×1 Lbottle centrifuge, Milford, Mass.) to reduce agglomerates. Specificamounts are listed in Table 13 for the starting materials used toprepare these products.

TABLE 13 POS 1c Nanoparticle Nanoparticle Product (Kg) Type Mass (g) 12a9.08 Diamond 18.60 12b 9.08 Silicon 7.57 Carbide

Example 13 Nanoparticle Hybrid Composite Material Surrounding of HybridParticles

To a suspension of 3.5 μm BEH porous hybrid particles (20 g, WatersCorporation, Milford, Mass.; 6.5% C; SSA=185 m²/g; SPV=0.76 cm³/g;APD=146 Å) of the formula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (preparedfollowing the method described in U.S. Pat. No. 6,686,035) in toluene(FISHER SCIENTIFIC™, Fairlawn, N.J.; 10 ml/g) was added a POS fromExample 12 (16.42 g) and deionized water (0.8 g). This reaction washeated at 80° C. for one hour and 110° C. for 20 hours using aDean-Stark trap to remove residual water. The reaction was cooled toroom temperature and particles were isolated on 0.5 μm filtration paperand washed repeatedly using ethanol (anhydrous, J.T.-BAKER™,Phillipsburgh, N.J.). The material was then heated to 50° C. in asuspension with ethanol (3 mL/g, anhydrous, J.T.-BAKER™, Phillipsburgh,N.J.), deionized water (7 ml/g) and 30% ammonium hydroxide (20 g; J.T.BAKER™, Phillipsburgh, N.J.) for 4 hours. The reaction was then cooledand the product was filtered and washed successively with water andmethanol (FISHER SCIENTIFIC™, Fairlawn, N.J.). The product was thendried at 80° C. under reduced pressure for 16 hours. The % C values,specific surface areas (SSA), specific pore volumes (SPV), average porediameters (APD) and changes in SPV (ΔSPV) of these materials are listedin Table 14.

This set of experiments showed that a nanoparticle containing POS can beused to create composite surrounding materials. This may allow formodification of particle properties (e.g., surface acidity, thermal andmechanical properties). A reduction in SPV (0.11 cm³/g) was achieved bythis composite Material Surrounding approach. SEM analysis confirmedequivalent particle morphology and surface features to that of thestarting particles. Particle size analysis (by COULTER COUNTER™, CoulterElectronics, Inc. Illinois) indicated equivalent particle size anddistribution of the starting particles. This suggests the decreasedporosity of this Material Surrounding process is due to a filling of theporous particle framework, and is not due to the introduction of surfacedebris or secondary nonporous particles.

TABLE 14 Particles Water % SSA SPV APD ΔSPV Product (g) POS (mL) C(m²/g) (cm³/g) (Å) (cm³/g) 13a 20 12a 0.8 6.42 199 0.65 137 −0.11 13b 2012b 0.8 6.47 204 0.65 136 −0.11

Example 14 Hydrothermal Processing of Nanoparticle Hybrid CompositeSurrounded Hybrid Particles

Hybrid particles from Examples 13b were mixed with an aqueous solutionof 0.3 M tris(hydroxymethyl)aminomethane (TRIS, ALDRICH™ Chemical,Milwaukee, Wis.) at a slurry concentration of 5 mL/g. The pH of theresultant slurry was adjusted to 9.8 using acetic acid (J.T. BAKER™,Phillipsburgh, N.J.). The slurry was then enclosed in a stainless steelautoclave and heated to 155° C. for 20 hours. After cooling theautoclave to room temperature, the product was isolated on 0.5 μmfiltration paper and washed with water and methanol (Fisher Scientific,Suwanee, Ga.). The particles were then dried at 80° C. under vacuum for16 hours. The resulting product 14a had 6.49% C, a specific surface area(SSA) of 132 m²/g, a specific pore volume of 0.64 cm³/g, and an averagepore diameter (APD) of 167 Å. Hydrothermal processing of a compositesurrounded hybrid material reduced SSA and increased APD without havinga significant changes in SPV or particle morphology (as determined bySEM) when compared with the precursor materials.

Example 15 Hybrid Inorganic/Organic Material Surrounding of Wider PoreHybrid Particles

To a suspension of wider pore BEH porous hybrid particles of the formula(O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (prepared following the methoddescribed in U.S. Pat. No. 6,686,035) denoted Type A (3.5 μm; 6.3% C;SSA=38 m²/g; SPV=0.67 cm³/g; APD=600 Å; MPV=0.67 cm³/g; MPD=513 Å), TypeB (3.5 μm; 6.6% C; SSA=83 m²/g; SPV=0.65 cm³/g; APD=287 Å; MPV=0.61cm³/g; MPD=243 Å), or Type C (5 μm; 6.44% C; SSA=95-100 m²/g;SPV=0.81-0.83 cm³/g; APD=289-324 Å; MPV=0.77-0.83 cm³/g; MPD=252-265 Å)in toluene (Fisher Scientific, Fairlawn, N.J.; 10 mL/g) was added a POSfrom Example 1 and deionized water. Reactions were heated at 80° C. forone hour and 110° C. for 20 hours. For reactions 15a and 15b aDean-Stark trap was used to remove residual water. The reaction wascooled to room temperature and particles were isolated on 0.5 μmfiltration paper and washed repeatedly using ethanol (anhydrous, J.T.BAKER™, Phillipsburgh, N.J.). The material was then heated 50° C. in asuspension with ethanol (3 mL/g, anhydrous, J.T.-BAKER™, Phillipsburgh,N.J.), deionized water (7 mL/g) and 30% ammonium hydroxide (20 g; J.T.BAKER™, Phillipsburgh, N.J.) for 4 hours. The reaction was then cooledand the product was filtered and washed successively with water andmethanol (FISHER SCIENTIFIC™, Fairlawn, N.J.). The product was thendried at 80° C. under reduced pressure for 16 hours. The % C values andspecific surface areas (SSA) of these materials are listed in Table 15.The median mesopore diameter (MPD) and mesopore pore volume (MPV),measured by Mercury Porosimetry are listed in Table 15. Changes inproduct SPV (ΔSPV) and MPV (ΔMPV), relative to the unmodified hybridparticles, are listed in Table 15.

This set of experiments showed that a hybrid POS can be used to createsurrounded wider pore diameter hybrid materials. This may allow formodification of particle surface properties, and mechanical properties.A reduction in pore volume may allow for improvements in mechanicalstrength of the porous network. Reduction in MPV (0.06-0.16 cm³/g) wereachieved by this composite Material Surrounding approach. SEM analysisconfirmed equivalent particle morphology and surface features of thestarting particles. Particle size analysis (by COULTER COUNTER™, CoulterElectronics, Inc. Illinois) indicated equivalent particle size anddistribution to that of the starting particles.

TABLE 15 POS Particle Particles mass Water SSA SPV APD ΔSPV MPV MPD ΔMPVProd. Type (g) POS (g) (g) % C (m²/g) (cm³/g) (Å) (cc/g) (cm³/g) (Å)(cc/g) 15a A 20 1c 16.4 0.82 6.29 54 0.30 251 −0.37 0.60 459 −0.07 15b B20 1c 16.4 0.82 6.53 98 0.58 260 −0.03 0.55 226 −0.06 15c C 10 1c 50.05.0 6.40 126 0.72 272 −0.11 0.68 227 −0.15 15d C 10 1c 50.0 5.0 6.42 1200.70 291 −0.13 0.67 231 −0.16 15e C 10 1c 50.0 2.5 6.48 114 0.72 276−0.11 0.68 231 −0.15 15f C 10 1c 50.0 0.4 6.63 116 0.79 303 −0.07 0.73239 −0.10 15g C 10 1c 50.0 0.4 6.48 111 0.75 301 −0.08 0.76 238 −0.0715h C 10 1c 8.2 5.0 6.48 117 0.72 295 −0.11 0.69 234 −0.14 15i C 10 1c8.2 2.5 6.66 114 0.76 303 −0.07 0.71 242 −0.12 15j C 20 1v 16.4 0.826.96 103 0.76 296 −0.03 0.73 235 −0.04 15k C 20 1w 16.4 0.82 8.02 950.74 301 −0.07 0.73 233 −0.64

Example 16 Hydrothermal Processing of Hybrid Surrounding Material withWider Pore Particles

Hybrid particles from Examples 15 were mixed with an aqueous solution of0.3 M tris(hydroxymethyl)aminomethane (TRIS, ALDRICH™ Chemical,Milwaukee, Wis.) at a slurry concentration of 5 mL/g. The pH of theresultant slurry was adjusted to 9.8 using acetic acid (J.T. BAKER™,Phillipsburgh, N.J.). The slurry was then enclosed in a stainless steelautoclave and heated to 155° C. for 20 hours. After cooling theautoclave to room temperature, the product was isolated on 0.5 μmfiltration paper and washed with water and methanol (FISHER SCIENTIFIC™,Suwanee, Ga.). The particles were then dried at 80° C. under vacuum for16 hours. Specific characterization data for these materials are listedin Table 16. Hydrothermal processing of a surrounding material withwider pore hybrid material reduced SSA and increased MPD without asignificant changes in % C or particle morphology (as determined by SEM)when compared with the precursor materials. A high resolution SEM ofproduct 16a indicates that a highly porous pore network is maintained bythis process.

TABLE 16 Δ□ SS Pre- SSA SPV APD A MPV MPD Product cursor % C (m²/g )(cm³/g) (Å) (m²/g ) (cm³/g) (Å) 16a 15a 6.27 37 0.27 290 −17 0.59 50016b 15b 6.55 73 0.58 293 −25 0.55 250 16c 15j 6.93 90 0.76 307 −13 0.72230 16d 15k 8.04 94 0.75 302  −1 0.73 237 16e 15c, 6.42 80 0.72 315 −390.70 254 15d 15e, 15h

Example 17 Acid Treatment of Hybrid Particles with Surrounding Material

Porous particles prepared according to Examples 5, 9 and 11 weredispersed in a 1 molar hydrochloric acid solution (ALDRICH™, Milwaukee,Wis.) for 20 h at 98° C. The particles were isolated on 0.5 μmfiltration paper and washed with water to a neutral pH, followed byacetone (HPLC grade, FISHER SCIENTIFIC™, Fairlawn, N.J.). The particleswere dried at 80° C. under vacuum for 16 h. Specific characterizationdata for these materials are listed in Table 17.

While no significant changes in SSA, SPV or APD occurred with respect tothe precursor materials, there are noticeable reductions in SSA (reduced13-63 m²/g) and SPV (reduced 0.05-0.23 cm3/g) with respect to theunmodified BEH hybrid particles.

With the exception of product 17k and 171, no significant changes in % Coccurred with respect to the precursor materials. The loss in % C forthese two products (reduced 0.41-0.75% C) may have resulted indeprotection of remaining tert-butoxycarbonyl groups, resulting in theformation of an aminopropyl group (e.g., NH₂(CH₂)₃SiO_(1.5)). Changes in% C, with respect to the unmodified BEH hybrid increased or decreaseddue to the chemical formula of the surrounding material. The microporesurface area (MSA) for these materials are all within the requirementfor chromatographic material having chromatographically enhanced poregeometry. Repeat experiments, products 17t-17x, demonstrate goodreproducibility with relative standard deviations for % C, SSA, SPV, andAPD less than 5%.

TABLE 17 dp₅₀ vol % 9/10 SSA SPV APD MSA Product Precursor (μm) ratio %C (m²/g) (cm³/g) (Å) (m²/g) 17a 5a 4.79 1.49 6.84 160 0.69 149 19 17b5h, 5i 3.72 1.48 7.16 161 0.66 144 24 17c 9d 3.47 1.46 7.30 149 0.67 15923 17d 9e 3.49 1.46 7.28 149 0.67 156 25 17e 9i 3.45 1.46 7.23 152 0.69160 26 17f 9j 3.53 1.46 7.23 160 0.69 147 21 17g 9k 3.55 1.46 7.48 1220.59 154 20 17h 9m 3.63 1.50 6.90 153 0.53 131 25 17i 9n 3.45 1.58 8.08178 0.71 144 20 17j 9o 3.51 1.54 7.49 170 0.70 150 22 17k 9p 3.45 1.647.53 147 0.66 157 15 17l 9q 3.36 1.61 7.68 156 0.73 166 18 17m 9r 3.451.62 7.80 161 0.67 147 17 17n 9s 3.43 1.61 8.50 163 0.68 146 13 17o 9t3.31 1.61 6.31 136 0.72 191 24 17p 11a 3.47 1.46 6.08 122 0.63 180 2817q 16c 4.74 1.47 6.97 91 0.77 307 17 17r 16d 4.73 1.51 7.98 94 0.75 29720 17s 16e 4.52 1.63 6.38 81 0.71 316 23 17t 9u 4.91 1.59 8.53 165 0.67140 12 17u 9v 4.89 1.61 8.63 164 0.66 140 12 17v 9w 2.99 1.56 8.49 1620.62 133 9 17w 9x 2.98 1.55 8.53 162 0.62 135 10 17x 9y 2.99 1.54 8.49161 0.61 134 13 17y 16b 3.31 1.54 6.46 73 0.55 178 18 17z 9z 2.97 1.548.55 163 0.62 134 14 17aa 9aa 3.53 1.64 8.36 162 0.66 143 12 17ab 9ab3.55 1.64 8.27 162 0.66 144 13 17ac 9ac 3.95 1.42 8.31 159 0.65 143 1217ad 9ad 4.84 1.60 8.35 154 0.64 140 8

Example 18 Reaction of Hybrid Particles with a Surrounding Material withIsocyanates

Hydroxypropyl containing Hybrid particles with a surrounding materialfrom Example 17 were modified with octadecyl isocyanate (ODIC, ALDRICH™Chemical), dodecyl isocyanate (DIC, ALDRICH™ Chemical),pentafluorophenyl isocyanate (PFPIC, ALDRICH™ Chemical), 1-adamantlyisocyanate (AIC, ALDRICH™ Chemical), 4-cyanophenyl isocyanate (4CPIC,ALDRICH™ Chemical), 3-cyanophenyl isocyanate (3CPIC, ALDRICH™ Chemical),4-biphenylyl isocyanate (BPIC, ALDRICH™ Chemical), 2,2-Diphenylethylisocyanate (DPEIC, ALDRICH™ Chemical), 3,5-dimethoxyphenyl isocyanate(DMPIC, ALDRICH™ Chemical), 4-iodophenyl isocyanate (IPIC, ALDRICH™Chemical), 4-(chloromethyl)phenyl isocyanate (CMPIC, ALDRICH™ Chemical),methyl (S)-(−)-2-isocyanato-3-phenylpropionate (MIP, ALDRICH™,Milwaukee, Wis.), phenyl isocyanate (PIC, ALDRICH™ Chemical), benzylisocyanate (BIC, ALDRICH™ Chemical), or phenethyl isocyanate (PEIC,Aldrich Chemical) in dry toluene (5 mL/g, J.T.-BAKER™) under an argonblanket. The suspension was heated to reflux (110° C.) for 16 h and thencooled to <30° C. Product 18g was prepared in refluxing xylenes (30mL/g, J.T. BAKER™). The particles were transferred to a filter apparatusand washed exhaustively with toluene and acetone. The material was thenheated for an hour at 50° C. in a 1:1 v/v mixture of acetone and 1%trifluoroacetic acid (ALDRICH™, Milwaukee, Wis.) solution (10 mL/gparticles, Hydrolysis type A), or in a 60:40 v/v mixture of acetone and100 mM ammonium bicarbonate (pH 8, ALDRICH™, Milwaukee, Wis.) for 20hours (Hydrolysis type B), or in a 60:40 v/v mixture of acetone and 100mM ammonium bicarbonate (pH 10, ALDRICH™, Milwaukee, Wis.) for 20 hours(Hydrolysis type C). Product 18r was heated for 1 hour. The reaction wasthen cooled and the product was filtered and washed successively withacetone and toluene (heated at 70° C.). The product was then dried at70° C. under reduced pressure for 16 hours. Reaction data is listed inTable 18. The surface coverage of carbamate groups was determined by thedifference in particle % C before and after the surface modification asmeasured by elemental analysis.

TABLE 18 Carbamate Isocyanate Surface Particles mass Coverage ProductPrecursor (g) Isocyanate (g) Hydrolysis % C (μmol/m²) 18a 17b 10 DIC 3.5A 8.36 0.59 18b 17b 10 MIP 3.3 A 8.36 0.65 18c 17i 10 DIC 5.0 A 11.821.76 18d 17j 5.4 DIC 2.5 A 10.47 1.44 18e 17m 9.5 DIC 4.8 A 12.49 2.4818f 17n 20 DIC 10.0 A 14.53 3.27 18g 17t, 17u 12 DIC 6.7 A 14.10 2.9618h 17v 50 DIC 25 A 14.53 3.29 18i 17v 50 ODIC 25 A 15.41 2.34 18j 17w110 ODIC 52.7 A 15.39 2.32 18k 17x 20 ODIC 9.52 A 15.16 2.26 18l 17v 10PFPIC 3.4 A 11.99 3.66 18m 17w 15 PFPIC 5.05 A 12.08 3.79 18n 17x 30PFPIC 10.10 A 12.16 3.39 18o 17x 20 AIC 5.71 A 10.96 1.36 18p 17x 204CPIC 4.64 A 13.08 3.69 18q 17x 20 BPIC 6.29 A 16.64 4.09 18r 17x 10ODIC 4.76 B 15.59 2.42 18s 17x 10 ODIC 4.76 B 15.64 2.44 18t 17x 20DPEIC 7.19 A 14.87 2.70 18u 17x 20 DMPIC 5.77 A 13.38 3.61 18v 17x 20IPIC 7.89 A 11.70 3.60 18w 17x 20 CMPIC 5.40 A 12.63 3.43 18x 17ab 20DIC 6.85 C 13.56 2.83 18y 17z 6 ODIC 1.44 B 12.31 1.20 18z 17z 6 ODIC2.31 B 13.57 1.64 18aa 17aa 20 ODIC 2.59 B 11.94 1.15 18ab 17aa 15 ODIC2.73 C 13.12 1.63 18ac 17aa 15 ODIC 5.46 C 14.61 2.20 18ad 17ac 25 4CPIC1.95 C 11.73 2.66 18ae 17z 30 4CPIC 7.05 A 13.08 3.60 18af 17ad 60 3CPIC4.59 C 12.03 3.03 18ag 17z 30 3CPIC 7.05 A 13.09 3.61 18ah 17z 20 PIC3.88 C 12.42 343 18ai 17aa 20 PEIC 4.77 C 11.92 2.43 18aj 17aa 20 BIC4.31 C 12.62 3.32 18ak 17aa 12 DPEIC 4.34 C 14.05 2.36 18al 17z 10 PFPIC3.41 B 11.89 3.46 18am 17z 10 PFPIC 1.16 B 11.68 3.22 18an 17z 15 PFPIC1.37 B 11.29 2.78 18ao 17z 10 PFPIC 1.16 B 11.53 3.05 18ap 17z 10 PFPIC0.92 B 11.34 2.84

Example 19 Secondary Surface Modification of Hybrid Particles with aSurrounding Material with Isocyanates

The materials of Example 18 were further modified with octadecylisocyanate (ODIC, ALDRICH™ Chemical), t-butyl isocyanate (TBIC, ALDRICH™Chemical), or n-butyl isocyanate (NBIC, ALDRICH™ Chemical) in drytoluene (5 mL/g, J.T.-BAKER™) under similar reaction conditions asExample 18. Reaction data is listed in Table 19. The additional surfacecoverage of carbamate groups was determined by the difference inparticle % C before and after the surface modification as measured byelemental analysis.

TABLE 19 Precursor Additional Carbamate Carbamate Surface IsocyanateSurface Coverage Particles mass Coverage Product Precursor (μmol/m²) (g)Isocyanate (g) % C (μmol/m²) 19a 18h 3.29 24 TBIC 3.85 14.52 nonedetermined 19b 18h 3.29 24 NBIC 3.85 14.77 0.36 19c 18i 2.34 24 ODIC11.5 16.56 0.44 19d 18j 2.34 10 PFPIC 3.39 16.30 1.25

Example 20 Modification of Hybrid Particles with a Surrounding Materialwith Chlorosilanes

The materials of Example 18 and 19 were further modified with eithertrimethylchlorosilane (TMCS, GELEST™ Inc., Morrisville, Pa.),triethylchlorosilane (TECS, GELEST™ Inc., Morrisville, Pa.),triisopropylchlorosilane (TIPCS, GELEST™ Inc., Morrisville, Pa.),thexyldimethylchlorosilane (TDMCS, GELEST™ Inc., Morrisville, Pa.),tert-butyldimethylchlorosilane (TBDMCS, GELEST™ Inc., Morrisvile, Pa.),1-(ert-Butyldimethylsilyl)imidazole (TBDMI, TC America), ortert-butyldiphenylchlorosilane (TBDPCS, GELEST™ Inc., Morrisville, Pa.)using imidazole (ALDRICH™, Milwaukee, Wis.) in refluxing toluene (5mL/g) for 4 hours. The reaction was then cooled and the product wasfiltered and washed successively with water, toluene, 1:1 v/vacetone/water and acetone (all solvents from J.T. BAKER™) and then driedat 80° C. under reduced pressure for 16 hours. Product 20f was performedfor 20 hours. Products 20f, 20i, 20j, 20k, and 20l underwent asubsequent reaction with TMCS under similar reaction conditions.Reaction data are listed in Table 20.

TABLE 20 Particles Silane Imidazole Product Precursor (g) Silane (g) (g)% C 20a 18a 9.3 TMCS 1.75 1.32 9.67 20b 18b 9.4 TMCS 1.65 1.24 9.57 20c18c 8.5 TMCS 1.65 1.24 12.95 20d 18e 7.1 TMCS 1.24 0.93 13.44 20e 18f17.3 TMCS 3.06 2.30 15.29 20f 18g 9.5 TBDMCS 2.36 1.28 14.78 20g 18i 21TMCS 4.22 3.18 16.42 20h 18j 20 TMCS 3.52 2.65 16.24 20i 18j 20 TECS4.88 2.37 16.24 20j 18j 20 TBDMCS 4.88 2.37 16.68 20k 18j 20 TIPCS 6.252.21 16.67 20l 18j 20 TDMCS 5.77 1.89 16.87 20m 18k 19 TMCS 3.32 2.5016.22 20n 18l 9.5 TMCS 1.67 1.26 12.26 20o 18m 13.7 TMCS 2.40 1.80 12.3520p 18n 15 TMCS 2.62 1.97 12.21 20q 18o 15.5 TMCS 2.71 2.04 12.35 20r18p 17.9 TMCS 3.13 2.35 13.62 20s 18q 20.0 TMCS 3.50 2.63 20.53 20t 19a21 TMCS 3.70 2.78 1527 20u 19b 21 TMCS 3.70 2.78 15.38 20v 19c 9.3 TMCS1.64 1.23 17.28 20w 19d 6.9 TMCS 1.21 0.91 16.51 20x 18r 6.3 TMCS 0.831.10 16.40 20y 18s 6.2 TMCS 1.08 0.82 16.52 20z 18t 16.9 TMCS 2.96 2.2215.60 20aa 18u 18.9 TMCS 3.31 2.49 13.86 20ab 18aa 19.0 TMCS 3.34 2.5113.20 20ac 18ae 15.0 TBDMCS 3.70 2.00 13.64 20ad 18ae 14.0 TBDMSI 4.161.86 13.03 20ae 18ag 15.0 TBDMCS 3.69 2.00 13.61 20af 18ag 15.0 TBDMSI4.46 2.00 13.32 20ag 18ah 17.4 TMCS 3.08 2.32 13.14 20ah 18aj 10.0TBDPCS 4.45 1.32 13.48 20ai 18al 8.0 TDMCS 2.33 1.07 12.41

Example 21 Initial Surface Modification of Hybrid Particles with aSurrounding Material with Chlorosilanes

Samples from Example 17 were modified with octadecyltrichlorosilane(OTCS, ALDRICH™, Milwaukee, Wis.) or octadecyldimethylchlorosilane(ODMCS, GELEST™ Inc., Morrisville, Pa.) using imidazole (ALDRICH™,Milwaukee, Wis.) in refluxing toluene (HPLC grade, FISHER SCIENTIFIC™,Fairlawn, N.J.) for 4 hours. The reaction was then cooled and theproduct was filtered and washed successively with toluene, 1:1 v/vacetone/water and acetone (all solvents from J.T. BAKER™). For product21a, the material was then refluxed in an acetone/aqueous 0.12 Mammonium acetate solution (Sigma Chemical Co., St. Louis, Mo.) for 2hours. The reaction was then cooled and the product was filtered andwashed successively with toluene, 1:1 v/v acetone/water and acetone (allsolvents from J.T. BAKER™). The product was then dried at 80° C. underreduced pressure for 16 hours. Reaction data is listed in Table 21. Thesurface coverage of C₁₈-groups was determined by the difference inparticle % C before and after the surface modification as measured byelemental analysis.

TABLE 21 Particles Silane Imidazole Toluene Coverage Prod. Precursor (g)Silane (g) (g) (mL) % C (μmol/m²) 21a 17p 15 OTCS 2.84 1.00 75 12.933.18 21b 17o 17 ODMCS 8.97 1.89 85 14.74 3.19 21c  17ad 20 TBDPCS 8.472.52 200 13.77 2.21

Example 22 Secondary Surface Modification of Hybrid Particles with aSurrounding Material with Chlorosilanes

The surface of the C₁₈-bonded hybrid material of Example 21a (14 g) wasfurther modified with triethylchlorosilane (2.76 g, TECS, Gelest Inc.,Morrisville, Pa.) using imidazole (1.50 g, ALDRICH™, Milwaukee, Wis.) inrefluxing toluene (75 mL) for 4 hours. The reaction was then cooled andthe product was filtered and washed successively with water, toluene,1:1 v/v acetone/water and acetone (all solvents from J.T. BAKER™) andthen dried at 80° C. under reduced pressure for 16 hours. The materialswere then mixed with hexamethyldisilazane (HMDS, Gelest Inc.,Morrisville, Pa.) yielding a slurry (concentration 1.1 g HMDS per 1.0 gparticles). The resultant slurry was then enclosed in a stainless steelautoclave and heated at 200° C. for 18 hours. After the autoclave cooledto room temperature the product was isolated on filtration paper andwashed successively with water, toluene, 1:1 v/v acetone/water andacetone (all solvents from J.T. BAKER™) and then dried at 80° C. underreduced pressure for 16 hours. The product (22a) had 14.04% C.

Example 23 Secondary Surface Modification of Hybrid Particles with aSurrounding Material with Chlorosilanes

The surface of the hybrid particle with a surrounding material fromExamples 17 and 21 were modified with trimethylchlorosilane (TMCS,GELEST™ Inc., Morrisville, Pa.) using imidazole (ALDRICH™, Milwaukee,Wis.) in refluxing toluene for 4 hours. The reaction was then cooled andthe product was filtered and washed successively with water, toluene,1:1 v/v acetone/water and acetone (all solvents from J.T. BAKER™) andthen dried at 80° C. under reduced pressure for 16 hours. Reaction dataare listed in Table 22.

TABLE 22 Particles TMCS Imidazole Toluene Product Precursor (g) (g) (g)(mL) % C 23a 17o 12 1.77 1.33 60 7.65 23b 21b 14 2.07 1.56 70 14.81

Example 24 Sub-1 μm Particle Containing Hybrid Inorganic/OrganicMaterial Surrounding of Hybrid Particles

To a suspension of 3.5 μm BEH porous hybrid particles (20 g, WatersCorporation, Milford, Mass.; 6.5% C; SSA=188 m²/g; SPV=0.78 cm³/g;APD=150 Å) of the formula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (preparedfollowing the method described in U.S. Pat. No. 6,686,035) in toluene(FISHER SCIENTIFIC™, Fairlawn, N.J.; 10 ml/g) was added a dispersion of<0.5 μm BEH porous hybrid particles within POS 1c from Example 1, andwater (0.82 mL). The dispersion of <0.5 μm BEH porous hybrid particles(particle size determined by SEM) within POS 1c was achieved forexamples 24a and 24b by stirring overnight. The dispersion for example24c required initial dilution in ethanol, followed by vacuumdistillation of ethanol. This Material Surrounding reaction was heatedat 80° C. for one hour and 110° C. for 20 hours. The reaction was cooledto room temperature and particles were isolated on 0.5 μm filtrationpaper and washed repeatedly using ethanol (anhydrous, J.T.-BAKER™,Phillipsburgh, N.J.). The material was then heated to 50° C. in asuspension with ethanol (3 mL/g, anhydrous, J.T.-BAKER™, Phillipsburgh,N.J.), deionized water (7 ml/g) and 30% ammonium hydroxide (20 g; J.T.BAKER™, Phillipsburgh, N.J.) for 4 hours. The reaction was then cooledand the product was filtered and washed successively with water andmethanol (FISHER SCIENTIFIC™, Fairlawn, N.J.). The product was thendried at 80° C. under reduced pressure for 16 hours. Specific amounts ofstarting materials used to prepare these products are listed in Table23. The % C values, specific surface areas (SSA), specific pore volumes(SPV), average pore diameters (APD) and change in SPV (ΔSPV) of thesematerials are listed in Table 23. SEM analysis indicated the presence ofsurface <0.5 μm particulates on the 3.5 μm particles.

TABLE 23 Par- Par- ticle ticle Addi- Addi- tive tive Size Mass POS SSASPV APD ΔSPV Product (μm) (g) (g) % C (m²/g) (cm³/g) (Å) (cm³/g) 24a0.17 0.5 16.42 6.68 207 0.65 138 −0.13 24b 0.30 0.5 16.42 6.63 196 0.65139 −0.13 24c 0.17 5.0 16.42 6.66 208 0.64 136 −0.14

Example 25 Acetoxypropyl Bondings on Hybrid Particles

To a suspension of BEH porous hybrid particles (Type A, WatersCorporation, Milford, Mass.; 6.5% C; SSA=190 m²/g; SPV=0.80 cm³/g;APD=155 Å) or 3 μm wider pore BEH porous particles (Type B, WatersCorporation, Milford, Mass.; 6.5% C; SSA=88 m²/g; SPV=0.68 cm³/g;APD=285 Å) of the formula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄ (preparedfollowing the method described in U.S. Pat. No. 6,686,035) in toluene(HPLC grade, FISHER SCIENTIFIC™, Fairlawn, N.J.) were modified with3-acetoxypropyltrichlorosilane (ATPTCS, Silar Laboratories, Scotia,N.Y.) and imidazole (ALDRICH™, Milwaukee, Wis.) and deionized water inrefluxing toluene (HPLC grade, FISHER SCIENTIFIC™, Fairlawn, N.J.) for20 hours. Reaction 25a used 5 μm particles, and Reactions 25g and 25hused 3.5 μm particles. The reaction was then cooled and the material wasfiltered and washed successively with toluene, 1:1 v/v acetone/water andacetone (all solvents from FISHER SCIENTIFIC™, Fairlawn, N.J.). Thematerial was then refluxed in an acetone/aqueous 0.12 M ammonium acetatesolution (Sigma Chemical Co., St. Louis, Mo.) for 2 hours. The reactionwas then cooled and the product was filtered and washed successivelywith toluene, 1:1 v/v acetone/water and acetone (all solvents from J.T.BAKER™). The product was then dried at 80° C. under reduced pressure for16 hours. The material was then dispersed in a 1 molar hydrochloric acidsolution (ALDRICH™, Milwaukee, Wis.) for 20 h at 98-100° C. to yieldhydroxypropyl groups (e.g., HO(CH₂)₃SiO_(1.5)), as confirmed by NMRspectroscopy. The particles were isolated on 0.5 μm filtration paper andwashed with water to a neutral pH, followed by acetone (HPLC grade,FISHER SCIENTIFIC™, Fairlawn, N.J.). The particles were dried at 80° C.under vacuum for 16 h. Reaction data is listed in Table 24. Product 25hwas also hydrothermally treated following the procedure in Experiment 9,and was acid treated following the procedure in Experiment 17. Thesurface coverage of hydroxypropyl groups was determined by thedifference in particle % C before and after the surface modification asmeasured by elemental analysis.

TABLE 24 Surface Cover- Par- Par- Imid- age ticle ticles ATPTCS azoleToluene Water % (μmol/ Prod. Type (g) (g) (g) (mL) (μL) C m²) 25a A 5020.73 0   250 0 7.79 2.80 25b B 15  3.11 0    75 0 7.08 2.80 25c B 15 3.11 0    75 7.5 7.30 3.37 25d B 15  3.11 0    75 15 7.23 3.08 25e B 15 3.04  1.05  75 7.5 7.42 4.34 25f B 15  3.04  1.05  75 15 7.42 4.34 25gA 50 20.73  7.55 250 25 8.40 3.28 25h A 50 32.15 11.15 250 50 8.18 3.30

Example 26 Reaction of Bonded Hybrid Particles with Isocyanates

Particles from Example 25a (20 g) were modified with octadecylisocyanate (9.99 g, ALDRICH™ Chemical) in dry toluene (100 mL, FISHERSCIENTIFIC™, Fairlawn, N.J.) under an argon blanket. The suspension washeated to reflux (110° C.) for 16 h and then cooled to <30° C. Theparticles were transferred to a filter apparatus and washed exhaustivelywith toluene and acetone. The material was then heated for an hour at50° C. in a 1:1 v/v mixture of acetone and 1% trifluoroacetic acid(ALDRICH™, Milwaukee, Wis.) solution (100 mL). The reaction was thencooled and the product was filtered and washed successively with acetoneand toluene (heated at 70° C.). The material was then dried at 70° C.under reduced pressure for 16 hours. The carbon content of this materialwas 13.32% C, and the surface coverage of carbamate groups was 1.73μmol/m², determined by the difference in % C before and after thesurface modification as measured by elemental analysis. The surface ofthese particles were modified with trimethylchlorosilane (TMCS, GELEST™Inc., Morrisville, Pa.) using imidazole (ALDRICH™, Milwaukee, Wis.) inrefluxing toluene for 4 hours.

The reaction was then cooled and the product was filtered and washedsuccessively with water, toluene, 1:1 v/v acetone/water and acetone (allsolvents from J.T. BAKER™) and then dried at 80° C. under reducedpressure for 16 hours. The final carbon content of the product (26a) was14.24% C.

Example 27 Chromatographic Evaluation of Porous Hybrid Particles with aSurrounding Maternal

Samples of porous particles from Example 18, 20, 23 and 26 were used forthe separation of a mixture of neutral, polar and basic compounds listedin Table 25. The 2.1×100 mm chromatographic columns were packed using aslurry packing technique. The chromatographic system consisted of anACQUITY UPLC® System and an ACQUITY UPLC® Tunable UV detector. Empower 2Chromatography Data Software (Build 2154) was used for data collectionand analysis. Mobile phase conditions were: 20 mM K₂HPO₄KH₂PO₄, pH7.00±0.02/methanol (36/65 v/v); flow rate: 0.25 mL/min; temperature:23.4° C.; detection: 254 nm.

It can be seen that these porous hybrid particles with a surroundingmaterial provide sufficient retention and resolution in the separationof neutral, polar, and basic compounds. Relative retention is theretention time of the analyte divided by the retention time ofacenaphthene. Therefore values less than one, indicate less retentionthan acenaphthene, and values greater than one, indicate more retentionthan acenaphthene. (Relative retention is a well-known parameter in thefield of HPLC.)

TABLE 25 Retention Relative Retention: Factor: Propranolol/Butylparaban/ Naphthalene Dipropylphthalate/ Amitriptyline/ SampleAcenaphthene Acenaphthene Acenaphthene Acenaphthene AcenaphtheneAcenaphthene Product 18d 1.86 1.094 0.454 0.576 0.543 3.484 Product 18n2.01 1.536 0.405 0.617 0.764 2.548 Product 20a 2.18 0.503 0.492 0.5830.692 1.757 Product 20c 4.65 0.251 0.406 0.523 0.485 1.228 Product 20d5.84 0.173 0.390 0.502 0.443 1.045 Product 20e 7.91 0.148 0.352 0.4820.387 0.952 Product 20f 8.60 0.161 0.332 0.478 0.395 0.986 Product 20g11.02 0.129 0.269 0.440 0.320 0.899 Product 20h 11.06 0.124 0.276 0.4490.324 0.869 Product 20i 11.00 0.123 0.271 0.443 0.321 0.872 Product 20j12.02 0.125 0.268 0.434 0.349 0.979 Product 20k 12.22 0.126 0.265 0.4410.332 0.960 Product 20l 11.63 0.128 0.273 0.438 0.342 0.979 Product 20n2.47 0.877 0.370 0.593 0.742 1.719 Product 20o 1.88 0.827 0.405 0.6150.768 1.709 Product 20p 1.83 0.909 0.401 0.621 0.753 1.826 Product 20q1.57 0.275 0.541 0.612 0.610 1.195 Product 20r 1.56 2.748 0.620 0.4870.428 4.734 Product 20s 8.34 0.238 0.233 0.430 0.696 2.113 Product 20t8.62 0.147 0.340 0.473 0.382 0.964 Product 20u 8.65 0.146 0.348 0.4820.387 0.965 Product 20v 13.40 0.113 0.239 0.433 0.288 0.829 Product 20w12.86 0.133 0.227 0.432 0.365 1.038 Product 20y 11.58 0.123 0.266 0.4440.317 0.846 Product 20z 3.64 0.267 0.353 0.525 0.739 1.544 Product 20aa1.86 0.240 0.328 0.617 0.655 1.062 Product 22a 1.34 0.772 0.487 0.6350.773 2.049 Product 23b 9.59 0.141 0.212 0.422 0.367 1.317 Product 26a7.67 0.145 0.321 0.469 0.381 0.969 Commercial 13.67 0.132 0.222 0.4200.403 1.240 <2 μm Hybrid C₁₈ Column Commercial 17.90 0.130 0.218 0.4150.393 1.256 <2 μm Silica C₁₈ Column Commercial 19.63 0.128 0.184 0.4120.343 1.227 3.5 μm Silica C₁₈ Column Commercial 12.57 0.181 0.283 0.4390.525 1.839 3.5 μm Silica C₁₈ Column

Example 28 Peak Shape Evaluation of Porous Hybrid Particles with aSurrounding Material

Samples of porous particles from Example 18, 20, 23 and 26 wereevaluated for USP peak tailing factors using the mobile phase and testconditions of Example 25. The results are shown in Table 26. Peaktailing factors is a well-known parameter in the field of HPLC (a lowervalue corresponds to reduced tailing). It is evident that the peaktailing factors these porous hybrid particles having a surroundingmaterial have comparable basic compound tailing factors of commerciallyavailable C₁₈-columns.

TABLE 26 Tailing Factor for: Sample Propranolol Butylparaben NaphthaleneDipropyphthalate Acenaphthene Amitriptyline Product 18d 1.55 1.01 1.030.94 0.95 1.33 Product 18n 4.72 1.02 1.08 0.93 1.09 3.41 Product 20a2.73 1.11 1.19 1.08 1.16 2.74 Product 20c 2.28 1.11 1.26 1.08 1.18 1.70Product 20d 0.98 1.23 1.25 1.22 1.23 1.23 Product 20e 0.83 1.19 1.211.17 1.17 1.12 Product 20f 1.30 0.99 1.09 0.98 1.06 1.07 Product 20g0.78 1.12 1.12 1.11 1.09 1.04 Product 20h 0.78 1.09 1.11 1.07 1.06 1.00Product 20i 0.88 1.15 1.16 1.15 1.11 1.09 Product 20j 0.82 1.13 1.181.12 1.12 1.06 Product 20k 0.80 1.12 1.22 1.11 1.15 1.06 Product 20l0.79 1.13 1.16 1.12 1.11 1.06 Product 20n 4.43 1.25 1.30 1.10 1.26 2.76Product 20o 3.21 1.18 1.18 1.09 1.17 3.00 Product 20p 5.63 1.11 1.051.04 1.14 4.12 Product 20q 0.91 1.03 1.17 1.05 1.20 1.10 Product 20r2.42 1.85 1.14 1.21 1.18 1.35 Product 20s 1.33 1.10 1.17 1.18 1.25 1.16Product 20t 0.79 1.12 1.14 1.10 1.12 1.05 Product 20u 0.76 1.11 1.131.08 1.10 1.02 Product 20v 0.83 1.18 1.18 1.17 1.15 1.10 Product 20w1.06 1.01 1.02 0.98 0.99 0.99 Product 20y 1.08 1.09 1.11 1.08 1.06 1.06Product 20z 0.80 1.13 1.20 1.25 1.20 1.23 Product 20aa 1.26 1.25 1.261.17 1.22 1.15 Product 22a 2.78 1.18 1.22 1.13 1.23 3.07 Product 23b1.01 1.36 1.25 1.35 1.23 1.40 Product 26a 1.15 1.25 1.28 1.28 1.26 1.30Commercial 0.81 1.13 1.05 1.11 1.02 1.41 <2 μm Hybrid C₁₈ ColumnCommercial 0.76 1.03 1.05 1.01 0.97 1.03 <2 μm Silica C₁₈ ColumnCommercial 1.37 1.15 1.07 1.08 1.03 2.01 3.5 μm Silica C₁₈ ColumnCommercial 1.12 1.22 1.17 1.21 1.13 3.89 3.5 μm Silica C₁₈ Column

Example 29 Chromatographic Evaluation of Porous Hybrid Particles Havinga Surrounding Material

Samples of porous particles from Example 9 and 17 were used for theseparation of a mixture of neutral, polar and basic compounds listed inTable 27. The 2.1×100 mm chromatographic columns were packed using aslurry packing technique. The chromatographic system consisted of anACQUITY UPLC® System and an ACQUITY UPLC® Tunable UV detector. Empower 2Chromatography Data Software (Build 2154) was used for data collectionand analysis. Mobile phase conditions were: 100 mM ammonium formate, pH0.3.00±0.02/acetonitrile (10/90 v/v); flow rate: 0.5 ml/min;temperature: 23.4° C.; detection: 254 nm. It can be seen that theseporous hybrid particles provide sufficient retention and resolution inthe separation of polar compound under Hydrophilic InteractionChromatography (HILIC) test conditions. Relative retention is theretention time of the analyte divided by the retention time of thymine.Therefore, values less than one, indicate less retention than thymine,and values greater than one, indicate more retention than acenaphthene.(Relative retention is a well-known parameter in the field of HPLC)t-Boc protected aminopropyl hybrid particles having a surroundingmaterial, 9q, showed low retention times for all analytes under thesetest conditions. This is expected due to the increased hydrophobicity ofthe t-Boc group. The deprotected aminopropyl surrounding hybridparticles, 171, resulted in a significant increase in retentivity.

TABLE 27 Relative Retention: Retention 5-Fluoroorotic Factor: Adenine/Cytosine/ Acid/ Sample Thymine Thymine Thymine Thymine Product 9q 0.0220.50 13.75 16.00 Product 17l 0.40 2.70 5.71 18.67 Product 17g 0.40 2.645.68 16.92 Product 17w 0.27 2.87 3.66 3.37 Commercial 3.5 μm 0.33 4.856.19 3.07 HILIC Column Commercial 3 μm 0.48 4.14 7.38 4.01 HILIC Column

Example 30 Peak Shape Evaluation of Porous Hybrid Particles with aSurrounding Material

Samples of porous particles from Example 9 and 17 were evaluated for USPpeak tailing factors using the mobile phase and test conditions ofExample 27. The results are shown in Table 28. Peak tailing factor is awell-known parameter in the field of HPLC (a lower value corresponds toreduced tailing). It is evident that the porous hybrid particles havinga surrounding material have comparable basic compound tailing factors ofcommercially available Hydrophilic Interaction Chromatography (HILIC)columns.

TABLE 28 Tailing Factor for: Acenaph- 5-Fluoroorotic Sample theneThymine Adenine Cytosine Acid Product 9q 1.19 1.40 1.55 1.43 2.14Product 17l 1.35 1.62 1.08 1.00 1.10 Product 17g 1.06 0.97 0.92 0.730.60 Product 17w 1.50 1.47 1.15 1.09 0.96 Commercial 1.05 0.96 0.90 0.881.09 3.5 μm HILIC Column Commercial 1.47 2.41 1.15 1.06 1.27 3 μm HILICColumn

Example 31 Low pH Chromatographic Stability Test

Surface derivatized hybrid porous particles from Examples 18, 20 and 26as well as selected commercial columns (C₁₈ Type) based on silica, whichhave similar alkyl silyl groups, were evaluated for stability in acidicmobile phases using the following procedure. Columns were prepared byslurry packing the materials into 2.1×50 mm steel columns and weretested on the following instrument configuration: Waters ACQUITY UPLC™system was used for solvent delivery, sample injection (1 μL on a 5 μLloop using partial loop injection), UV detection (500 nL flow cell,Absorbance: 254 nm) and column heating at 60° C. Analysis conditionswere as follows: 1) the retention time was measured for a test analyte,methyl paraben (100 μg/mL sample); 2) mobile phase conditions were 0.5%aqueous TFA at a flow of 1.4 mL/min and a column temperature of 60° C.;and 3) 20 minute run times for 61 repeated injections under the sameisocratic test conditions were used. The percent changes in theretention time are reported for final injections for methyl paraben,with respect to the retention obtained on the third injection. Theresults are shown in Table 29.

It is evident that the lifetimes of most of the columns containinghybrid particles having a surrounding material had similar chemicalstability with respect to commercial columns containing silica-basedmaterials (lower percent loss in original retention for each injectioncorresponds to improved chemical stability).

TABLE 29 Loss in original retention time after 20.3 h Column of exposureto 0.5% TFA Commercial 3.5 μm Silica C₁₈ 16.6%  Column Commercial 3.5 μmSilica C₁₈ 13.7%  Column Commercial 3 μm Silica C₁₈ 9.4% Column Product18n 5.4% Product 20e 12.2%  Product 20f 6.7% Product 20g 8.5% Product20h 9.5% Product 20i −2.7%   Product 20j 2.0% Product 20k 4.0% Product20l −7.0%   Product 20m 10.5%  Product 20n 19.7%  Product 20o 25.9% Product 20p 24.9%  Product 20r 17.7%  Product 20s 21.8%  Product 20t12.1%  Product 20u 7.1% Product 20v 7.4% Product 20w 6.5% Product 20z25.8%  Product 20aa 19.2%  Product 26a 19.0% 

Example 32 Hydrolytic Stability Test

The hydrolytic stability of the columns packed with porous hybridparticles from Example 17, 18, 20, 22, and 26 as well as some comparisoncolumns were evaluated using the following procedure. Columns (3×30 mm)were equilibrated in 1:1 acetonitrile/water (210 minutes) before initialchromatographic performance was tested using uracil and decanophenone(1:1 acetonitrile/water; 0.43 mL/min). The columns were then heated at50° C. and were challenged with a solution of 0.02 N NaOH in water (pH12.3, 0.85 mL/min for 60 min) before flushing with 10:90 methanol/waterfollowed by methanol. Chromatographic performance was reassessed atregular intervals by equilibrating the columns with acetonitrile (50minutes), followed by testing using uracil and decanophenone (1:1acetonitrile/water or 0.1% formic acid in 30:70 methanol/water, 0.43mL/min). This process was repeated and the performance of the column wasmonitored until column failure. Column failure is defined as the timewhen the plate number drops to 50% of the initial value or when the testsystem shut down due to high column pressure. The results of thesetests, including final reported loss in original column efficiency areshown in Table 30. Comparison Column A was commercially available 5 μmporous hybrid particles of the formula(O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄, that was surface modified withC₁₈H₃₇SiCl₃ followed by endcapping. Comparison Column B (repeated onthree separate columns) was 3.5 μm porous hybrid particles of theformula (O_(1.5)SiCH₂CH₂SiO_(1.5))(SiO₂)₄, that was surface modifiedwith CH₃(CH₂)₁₁NHCO₂(CH₂)₃Si(CH₃)₂Cl followed by endcapping. ComparisonColumn C was a commercially available 3 μm silica-core particle that wassurface modified with an organofunctional silane followed by C₁₈ surfacemodification. Comparison Column D was commercially available 5 μm poroushybrid particles of the formula (CH₃SiO_(1.5))(SiO₂)₂, that was surfacemodified with C₁₈H₃₇SiCl₃ followed by endcapping. Comparison Column Ewas commercially available 5 μm porous silica particles that was surfacemodified with C₁₈H₃₇Si(CH₃)₂Cl followed by endcapping.

Comparison Column A and B (which is based on a hybrid formula that issubstantially enriched in silica content) failed under these testconditions between 22-52 hours exposure to 0.02 N NaOH. Hybrid Column Efailed within 3 hours exposure to 0.02 N NaOH. Comparison Column C and E(which are based on a silica base particle) failed under these testconditions at 3-5 hours exposure to 0.02 N NaOH. It is well known in thefield of HPLC that column failure resulting in high column pressure whensilica based columns are exposed to alkaline solutions can result fromthe dissolution of the silica particle resulting in the collapse of thecolumn bed. For Comparison Column B this packed-bed collapse wasconfirmed by column dissection and the measurement of a 10 mm void atthe inlet of the column.

It can be concluded that the durability of the porous hybrid packingmaterials from Example 17, 20 and 22 are improved over the bothComparison Columns C, D, and E, and are comparable to Comparison ColumnsA and B under these test conditions.

TABLE 30 Exposure Time to Loss in original Column 0.02N NaOH (h) Columnefficiency Comparison Column A 52 53% Comparison Column B 22 55%Comparison Column C 5 high pressure Comparison Column D 5 50% ComparisonColumn E 3 64% Product 17c 25 54% Product 17e 24 High pressure Product18n 11 50% Product 20c 19 56% Product 20e 26 51% Product 20f 34 54%Product 20g 16 52% Product 20h 23 55% Product 20i 23 70% Product 20j 3354% Product 20k 31 57% Product 20l 32 56% Product 20n 17 71% Product 20o10 51% Product 20p 8 51% Product 20r 11 51% Product 20s 23 64% Product20t 25 55% Product 20u 24 55% Product 20v 24 61% Product 20w 23 55%Product 20z 24 60% Product 20aa 22 60% Product 22a 49 51% Product 26a 1052%

Example 33 Selectivity Comparison of Surrounding Porous Hybrid ParticlesHaving a Surrounding Material with a Commercial C18 Column

Chromatographic selectivity differences for select products from Example18 and 20 were evaluated under pH 7 and pH 3 test conditions (2.1×100 mmcolumns). System conditions were the same as detailed in Experiment 27.Mobile phase conditions were: 20 mM K₂HPO₄/KH₂PO₄, pH 7.00±0.02/methanol(36/65 v/v) or 15.4 mM ammonium formate, pH 3.0/acetonitrile (65/35v/v); flow rate: 0.25 mL/min, temperature: 23° C.; detection: 254 nm. pH7 test molecules included uracil, propranolol, butylparaben,naphthalene, dipropylphthalate, acenaphthene, and amitriptyline. pH 3test molecules included uracil, pyrenesulfonic acid, desipramine,amitriptyline, butylparaben, and toluene. The correlation coefficient(R²) for retention times were made with a commercially available C18column (XBridge C18, Waters Corporation) under both pH 7 and pH 3 testconditions. The selectivity value was calculated by 100(1−R²)^(0.5) asshown in Table 31. A lower R² and higher Selectivity Value indicate agreater selectivity difference under these test conditions. It can beconcluded that surface modification of hybrid particles under conditionsused in Examples 18 and 20 provide a different chromatographicselectivity under these test conditions.

TABLE 31 pH 7 pH 7 pH 3 pH 3 Correlation Selectivity CorrelationSelectivity Sample (R²) Value (R²) Value Product 18n 0.401 77.4 0.62161.5 Product 20m 0.910 30.0 0.886 33.7 Product 20o 0.727 52.3 0.002 99.9Product 20p 0.674 57.1 0.025 98.7 Product 20q 0.960 20.0 0.673 57.2Product 20r 0.285 84.6 0.419 76.2 Product 20s 0.867 36.5 0.973 16.5Product 20z 0.928 26.7 0.900 31.6 Product 20aa 0.922 27.9 0.953 21.6

Example 34 Reaction of Chloromethylphenyl containing Porous HybridParticles with a Surrounding Material with Piperazine

Chloromethylphenyl containing particles 18w from Experiment 18 werefurther modified with piperazine (Acros, Geel Belgium) in refluxingtoluene (110° C., HPLC grade, FISHER SCIENTIFIC™, Fairlawn, N.J.) for 20hours. The reaction was then cooled and the material was filtered andwashed successively with toluene, 1:1 v/v acetone/water and acetone (allsolvents from J.T. BAKER™). The product was then dried at 80° C. underreduced pressure for 16 hours. Reaction data is listed in Table 32. Thesurface coverage of piperazyl groups (e.g.,O_(1.5)Si(CH₂)₃OC(O)NHC₆H₄CH₂N(CH₂CH₂)₂NH) was determined by thedifference in particle % C before and after the surface modification asmeasured by elemental analysis.

TABLE 32 Piperazine Particles Piperazine Toluene % % coverage Product(g) (g) (mL) C N (μmol/m²) 34a 2 0.3 10 13.52 1.22 2.80

Example 35 Reaction of Propanol Containing Porous Hybrid Particles witha Surrounding Material Using 1,1′-Carbonyldiimidazole

Propanol containing hybrid particles from Example 17 were modified with1,1′-carbonyldiimidazole (CDI, Fluka, Buchs, Switzerland) in toluene(Tol, 5 mL/g,—FISHER SCIENTIFIC™, Fairlawn, N.J.) for 2 hours at roomtemperature, or in dimethylformamide (DMF, 5 mL/g, ALDRICH™) for 20hours at room temperature. Reactions performed in toluene weretransferred to a filter apparatus and washed exhaustively with toluene,before redispersing in toluene. Octadecylamine (ODA, Fluka), octylamine(OA, ALDRICH™), 4-aminophenol (AP, ALDRICH™),tris(hydroxymethyl)methylamine (TRIS, ALDRICH™, dissolved in DMF at 60°C.), or pentafluorophenylamine (PFPA, ALDRICH™) was then added and thereaction was stirred for an additional 20 hours. Specific reactionconditions are provided in Table 33. The product was filtered and washedsuccessively with acetone, toluene, water and/or DMF. The material wasthen dried at 70° C. under reduced pressure for 16 hours. Product 35band 35c were further heated for an hour at 50° C. in a 1:1 v/v mixtureof acetone and 1% trifluoroacetic acid (ALDRICH™, Milwaukee, Wis.)solution (10 mL/g particles), and products 35f and 35g were furtherheated for 20 hours at 50° C. in a 60:40 v/v mixture of acetone and 100mM ammonium bicarbonate (pH 8, ALDRICH™, Milwaukee, Wis.). The reactionwas then cooled and the product was filtered and washed successivelywith acetone and toluene (heated at 70° C.). The product was then driedat 70° C. under reduced pressure for 16 hours. Product data is listed inTable 33. Product 35e was obtained by repeating this process on product35d. The surface coverage of carbamate groups was determined by thedifference in particle % C before and after the surface modification asmeasured by elemental analysis.

TABLE 33 Carbamate Particles CDI Solvent Amine Temp. % Coverage ProductPrecursor (g) (g) Solvent (mL) Amine (g) (° C.) C (μmol/m²) 35a 17w 20.63 Tol 10 ODA 1.51 25 13.12 3.23 35b 17x 20 6.27 Tol 100 OA 31.24 2517.01 3.11 35c 17x 15 4.70 Tol 75 AP 9.49 25 9.10 0.53 35d 17w 20 6.30DMF 100 TRIS 14.13 60 9.79 1.70 35e 35d 10 3.15 DMF 50 TRIS 7.06 6010.32 2.46 35f 17z 15 4.76 Tol 75 PFPA 16.11 110 9.04 0.49 35g 17z 206.34 Tol 100 PFPA 21.5 110 9.1 0.55

Example 36 Hybrid Monolith with a Surrounding Material

Hybrid inorganic/organic monoliths of the formula(O_(1.5)SiCH₂CH₂Si_(1.5)))(SiO₂)₄ (which is prepared following themethod described in U.S. Pat. No. 7,250,214) are soaked in toluene (J.T.BAKER™, 20 mL/g) and refluxed for 3.5 hours under an argon atmosphere todeoxygenate and to remove adsorbed water via azeotropic distillation.After cooling to room temperature under, POS 1c from Example 1 (0.8-1.6g/g) and deionized water (0.04-0.2 mL/g) is added. The reaction isheated at 80° C. for one hour and 110° C. for 20 hours using aDean-Stark trap to remove residual water. Alternatively, the Dean-Starktrap is not employed to remove residual water from the reaction. Thereaction is cooled to room temperature and monoliths are washedrepeatedly using ethanol (anhydrous, J.T.-BAKER™, Phillipsburgh, N.J.).

The material is then heated at 50° C. in a suspension with ethanol (3mL/g, anhydrous, J.T. BAKER™, Phillipsburgh, N.J.), deionized water (7mL/g) and 30% ammonium hydroxide (20 g; J.T. BAKER™, Phillipsburgh,N.J.) for 4 hours. The reaction is then cooled and the product is washedsuccessively with water and methanol (FISHER SCIENTIFIC™, Fairlawn,N.J.). The product is dried at 80° C. under reduced pressure for 16hours.

This Material Surrounding of hybrid inorganic/organic monoliths can beperformed using a variety of hybrid inorganic/organic POS' from Example1 (1a-1x), nanoparticle containing POS from Example 12, or sub-1 μmparticle containing POS as detailed in Example 24. Silica hybridmonoliths with a surrounding material can also be prepared using POS 1yfrom Example 1. This Material Surrounding of hybrid inorganic/organicmonoliths can be performed in a reactor, or within a chromatographicdevice (e.g., microbore tubes, extraction cartridges, capillary tubes)under a pressurized flow of solvent and reagents, or it can be performedunder stop-flow conditions. This Material Surrounding can be performedusing a variety of hybrid monoliths, including other hybrid monolithsdetailed in U.S. Pat. No. 7,250,214, hybrid monoliths prepared from thecondensation of one or more monomers that contain 0-99 mole percentsilica (e.g., SiO₂), hybrid monoliths prepared from coalesced porousinorganic/organic particles (also detailed in U.S. Pat. No. 7,250,214),hybrid monoliths that have a chromatographically-enhancing poregeometry, hybrid monoliths that do not have achromatographically-enhancing pore geometry, hybrid monoliths that haveordered pore structure, hybrid monoliths that have non-periodic porestructure, hybrid monoliths that have non-crystalline or amorphousmolecular ordering, hybrid monoliths that have crystalline domains orregions, hybrid monoliths with a variety of different macropore andmesopore properties, and hybrid monoliths in a variety of differentaspect ratios.

Example 37 Formation of Hybrid Monoliths with Porous Hybrid ParticlesHaving a Surrounding Material

Hybrid inorganic/organic particles having a surrounding material fromExamples 8-11 and Examples 13-24 are mixed with 5 μm Symmetry silica(Waters Corporation, 0-50% weight) to yield 6 g total mass. The mixtureis dispersed in an appropriate solvent (e.g.,isopropanol/tetrahydrofuran mixtures) for 5 minutes, before slurrypacking into 2.1×50 mm HPLC columns using a downward slurry techniquewith a high-pressure liquid packing pump. After completion of columnpacking, the pressure is released and the end fitted column istransferred to chromatographic pump station (Waters 590 HPLC pump orequivalent), whereupon the column is purged with dry toluene (J.T.BAKER™, 0.2 mL/min), before pumping (0.2 mL/min) a solution of POS 1cfrom Example 1 (0.8 g per gram of particle mixture) and water (0.04 mLper gram of particle mixture) that is pre-diluted in toluene. Thesereactions can use short (less than 1 hour) or extended flow times (lessthan 72 hours) to aid in monolith formation. The column pressure isallowed to drop for 30 minutes prior to disconnection. The columns areleft uncapped in a chemical fume hood's air stream for 5-18 hours,transferred to a 65° C. convection oven for 28 hours and then cooled toroom temperature. Analysis of these hybrid monoliths (SSA, SPV, APD, %C, SEM, mercury porosimetry) is performed on samples that are extrudedfrom the columns and are vacuum dried for a minimum of 8 hours at roomtemperature.

This monolith formation of hybrid inorganic/organic particles isperformed using a variety of hybrid inorganic/organic POS from Example 1(1a-1x), nanoparticle containing POS from Example 12, or sub-1 μmparticle containing POS as detailed in Example 24. To increase themacropore volume of this monolith, the silica template may be removedthrough purging the column with solutions of aqueous sodium hydroxide ortrimethyl amine. Alternatively, the silica particle may be replaced withappropriately sized polystyrene latex. For this alternative monolithsystem, solvents that do not swell or dissolve the polystyrene latexmust be employed (e.g., a polar protic solvent, or the pumping of a POSfrom Example 1 with or without additional water present). Upon formationof the coalesced hybrid particle monolith, the polystyrene particles canbe removed thermally or by purging the column with toluene. Thermalremoval of polystyrene can be aided with an inert atmosphere purge(nitrogen or argon) or the use of vacuum.

Example 38 Hydrothermal Processing of Surrounded Hybrid Monoliths

A monolith from Examples 36 or 37 is mixed with an aqueous solution of0.3 M tris(hydroxymethyl)aminomethane (TRIS, ALDRICH™ Chemical,Milwaukee, Wis.) at a concentration of 5 mL/g, and the pH is adjusted to9.8 using acetic acid (J.T. BAKER™, Phillipsburgh, N.J.). The monolithis enclosed in a stainless steel autoclave and is heated to 155° C. for20 hours. After cooling the autoclave to room temperature, the productis washed with water and methanol (FISHER SCIENTIFIC™, Suwanee, Ga.),and is dried at 80° C. under vacuum for 16 hours. Products prepared inthis manner have chromatographically enhanced pore geometry.

Example 39 Surface Modification of Surrounded Hybrid Monoliths

A monolith from Examples 36, 37 or 38 is treated with a 1 molarhydrochloric acid solution (ALDRICH™, Milwaukee, Wis.) for 20 h at 98°C. After cooling the product is washed with water to a neutral pH,followed by acetone (HPLC grade, FISHER SCIENTIFIC™, Fairlawn, N.J.).The monolith is dried at 80° C. under vacuum for 16 h. Surface silanolgroups of these surrounded hybrid monoliths can be modified in a similarmanner as shown in Examples 20-22 by reaction with chlorosilanes. Hybridmonoliths containing surface hydroxypropyl groups can be modified in asimilar manner as shown in Example 18-19 by reaction with isocyanates.Other transformations of synthetically relevant hybrid groups have beenreported in U.S. Pat. No. 7,250,214. Chromatographic evaluation ofsurface modified hybrid monoliths having a surrounding material preparedin chromatographic columns can be performed in a similar manner asdetailed in Examples 27-30. Chemical stability tests can also beperformed as detailed in Examples 31-32.

Example 40 Reaction of Bonded Hybrid Particles with Isocyanates

Following the procedure in Example 26, products 25g and 25h were reactedwith octadecyl isocyanate, followed by endcapping withtrimethylchlorosilane. Product data is shown in Table 34.

TABLE 34 Carbamate Particles Coverage Endcap Product Precursor (g) % C(μmol/m²) % C 40a 25g 25 14.80 2.00 15.29 40b 25h 18 16.04 2.54 16.75

Example 41 Reaction of Bonded Hybrid Particles with Isocyanates

Following the general procedure in Example 26, product 25a-h reacts with4-cyanophenyl isocyanate, 3-cyanophenyl isocyanate, or 2-cyanophenylisocyanate. Hydrolysis type A, B, or C from Example 18 is preformed.Products prepared by this manner can be endcapped or used without anyfurther transformation.

INCORPORATION BY REFERENCE

The entire contents of all patents published patent applications andother references cited herein are hereby expressly incorporated hereinin their entireties by reference.

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, numerous equivalents to thespecific procedures described herein. Such equivalents are considered tobe within the scope of this invention and are covered by the followingclaims.

1. An inorganic/organic hybrid material comprising an inorganic/organichybrid surrounding material and an inorganic/organic hybrid core;wherein the inorganic/organic hybrid surrounding material comprises amaterial of a formula selected from the group consisting of formula I:(SiO₂)_(d)/[R²((R)_(p)(R¹)_(q)SiO_(t))_(m)];  (I) wherein, R and R¹ areeach independently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl; R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl,C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl,C₁-C₁₈ heteroaryl, wherein each R² is attached to two or more siliconatoms; p and q are each independently 0.0 to 2.0; t is 0.5, 1.0, or 1.5;d is 0 to about 30; m is an integer from 2-20;$t = \frac{\left( {3 - \left( {p + q} \right)} \right)}{2}$ and p+q≤2;formula II:(SiO₂)_(d)/[(R)_(p)(R¹)SiO_(t)]  (II); wherein, R and R¹ are eachindependently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₂-C₅ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl; d is 0 to about 30; p and q are eachindependently 0.0 to 3.0, provided that p+q=1, 2, or 3; wherein whenp+q=1, then t=1.5; when p+q=2, then t=1; and when p+q=3, then t=0.5;formula III:(SiO₂)_(d)/[R²((R¹)SiO_(t))_(m)]  (III) wherein, R¹ is C₁-C₁g alkoxy,C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁sheterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈ heteroaryl; R²is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl; wherein each R²is attached to two or more silicon atoms; d is 0 to about 30; r is 0, 1or 2, wherein when r=0 then t=1.5; or when r=1 then t=1; or when r=2then t=0.5; and m is an integer from 1-20; formula IV:(A)_(x)(B)_(y)(C)_(z)  (IV), wherein the order of repeat units A, B, andC may be random, block, or a combination of random and block; A is anorganic repeat unit which is covalently bonded to one or more repeatunits A or B via an organic bond; B is an organosiloxane repeat unitwhich is bonded to one or more repeat units B or C via an inorganicsiloxane bond and which may be further bonded to one or more repeatunits A or B via an organic bond; C is an inorganic repeat unit which isbonded to one or more repeat units B or C via an inorganic bond; and xand y are positive numbers and z is a non-negative number, wherein whenz=0, then 0.002≤x/y≤210, and when z≠0, then 0.0003≤y/z≤500 and0.002≤x/(y+z)<210; and formula V:(A)_(x)(B)_(y)(B*)_(y)*(C)_(z)  (V), wherein the order of repeat unitsA, B, B*, and C may be random, block, or a combination of random andblock; A is an organic repeat unit which is covalently bonded to one ormore repeat units A or B via an organic bond; B is an organosiloxanerepeat units which is bonded to one or more repeat units B or B* or Cvia an inorganic siloxane bond and which may be further bonded to one ormore repeat units A or B via an organic bond; B* is an organosiloxanerepeat unit which is bonded to one or more repeat units B or B* or C viaan inorganic siloxane bond, wherein B* is an organosiloxane repeat unitthat does not have reactive organic components and may further have aprotected functional group that may be deprotected after polymerization;C is an inorganic repeat unit which is bonded to one or more repeatunits B or B* or C via an inorganic bond; and x and y and y* arepositive numbers and z is a non-negative number, wherein when z=0, then0.002≤x/(y+y*)≤210, and when z≠0, then 0.0003≤(y+y*)/z≤500 and0.002≤x/(y+y*+z)≤210; wherein the inorganic/organic hybrid core has aformula selected from the group consisting of formula II:(SiO₂)_(d)1[(R)_(p)(R¹)SiO_(t)]  (II); wherein, R and R¹ are eachindependently C₁-C₁₈ alkoxy, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈alkynyl, C₃-C₁₈ cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈aryloxy, or C₁-C₁₈ heteroaryl; d is 0 to about 30; p and q are eachindependently 0.0 to 3.0, provided that p+q=1, 2, or 3; wherein whenp+q=1, then t=1.5; when p+q=2, then t=1; and when p+q=3, then t=0.5;formula III:(SiO₂)_(d)/[R²((R¹)_(r)SiO_(t))_(m)]  (III) wherein, R¹ is C₁-C₁galkoxy, C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈ cycloalkyl,C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₅-C₁₈ aryloxy, or C₁-C₁₈heteroaryl; R² is C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, C₂-C₁₈ alkynyl, C₃-C₁₈cycloalkyl, C₁-C₁₈ heterocycloalkyl, C₅-C₁₈ aryl, C₁-C₁₈ heteroaryl;wherein each R² is attached to two or more silicon atoms; d is 0 toabout 30; r is 0, 1 or 2, wherein when r=0 then t=1.5; or when r=1 thent=1; or when r=2 then t=0.5; and m is an integer from 1-20; formula IV:(A)_(x)(B)_(y)(C)_(z)  (IV), wherein the order of repeat units A, B, andC may be random, block, or a combination of random and block; A is anorganic repeat unit which is covalently bonded to one or more repeatunits A or B via an organic bond; B is an organosiloxane repeat unitwhich is bonded to one or more repeat units B or C via an inorganicsiloxane bond and which may be further bonded to one or more repeatunits A or B via an organic bond; C is an inorganic repeat unit which isbonded to one or more repeat units B or C via an inorganic bond; and xand y are positive numbers and z is a non-negative number, wherein whenz=0, then 0.002≤x/y≤210, and when z≠0, then 0.0003≤y/z≤500 and0.002≤x/(y+z)<210; and formula V:(A)_(x)(B)_(y)(B*)_(y)*(C)_(z)  (V), wherein the order of repeat unitsA, B, B*, and C may be random, block, or a combination of random andblock; A is an organic repeat unit which is covalently bonded to one ormore repeat units A or B via an organic bond; B is an organosiloxanerepeat units which is bonded to one or more repeat units B or B* or Cvia an inorganic siloxane bond and which may be further bonded to one ormore repeat units A or B via an organic bond; B* is an organosiloxanerepeat unit which is bonded to one or more repeat units B or B* or C viaan inorganic siloxane bond, wherein B* is an organosiloxane repeat unitthat does not have reactive organic components and may further have aprotected functional group that may be deprotected after polymerization;C is an inorganic repeat unit which is bonded to one or more repeatunits B or B* or C via an inorganic bond; and x and y and y* arepositive numbers and z is a non negative number, wherein when z=0, then0.002≤x/(y+y*)≤210, and when z≠0, then 0.0003≤(y+y*)/z≤500 and0.002≤x/(y+y*+z)≤210; wherein the inorganic/organic hybrid surroundingmaterial and the inorganic/organic hybrid core are composed of differentmaterials.
 2. The inorganic/organic hybrid material of claim 1, whereina pore structure of the inorganic/organic surrounding material comprisesan ordered pore structure.
 3. The inorganic/organic hybrid material ofclaim 1, wherein the inorganic/organic surrounding material has achromatographically enhancing pore geometry (CEPG).
 4. A separationsdevice having a stationary phase comprising the inorganic/organic hybridmaterial of claim
 1. 5. The separations device of claim 4, wherein saiddevice is selected from the group consisting of chromatographic columns,thin layer plates, filtration membranes, sample cleanup devices, solidsupports, microchip separation devices, and microtiter plates, whereinthe separations device preferably is useful for applications selectedfrom the group consisting of solid phase extraction, high pressureliquid chromatography, ultra-high liquid chromatography, combinatorialchemistry, synthesis, biological assays, mass spectrometry, normal-phaseseparations, reversed-phase separations, HILIC separations, SFCseparations, affinity separations, and SEC separations.
 6. Achromatographic column, comprising a) a column having a cylindricalinterior for accepting a packing material and b) a packedchromatographic bed comprising the inorganic/organic hybrid material ofclaim 1.